Regioselective Synthesis of 2-Acylbutadienes from β,γ-Unsaturated Ketones

Article abstract of DOI:10.1055/s-0039-1690003

2-Acylbuta-1,3-dienes have been synthesized regioselectively from aromatic and heteroaromatic β,γ-unsaturated ketones (readily accessible via base-catalyzed addition of ketones to acetylenes) and aldehydes. The reaction smoothly proceeds with piperidine (

Full text of DOI:10.1055/s-0039-1690003

SYNTHESIS
0
0
3
9
-
7
8
8
1
1
4
3
7
-
2
1
0
X
© Georg Thieme Verlag Stuttgart · New York
2019, 51, A–I
paper
A
en
D. A. Shabalin et al.
Paper
Synthesis
Regioselective Synthesis of 2-Acylbutadienes from ,-Unsaturated
Ketones
Dmitrii A. Shabalin
Elena V. Ivanova
Igor’ A. Ushakov
Elena Yu. Schmidt
Boris A. Trofimov*
A. E. Favorsky Irkutsk Institute of Chemistry, Siberian Branch of
the Russian Academy of Sciences, 1 Favorsky St, Irkutsk
664033, Russian Federation
boris_trofimov@irioch.irk.ru
Received: 28.05.2019
Accepted after revision: 26.06.2019
Published online: 15.07.2019
Over the past decade, carbon nucleophiles derived from
,-unsaturated ketones (allyl ketones) have been exten-
sively studied in vinylogous reactions with diverse -elec-
trophiles,4 namely carbonyl compounds,5 imines,6 activated
alkenes7 and alkynes.8 It is noteworthy that these studies
are focused on regio-, diastereo-, and enantioselective syn-
theses of aldol-type products and mainly concern the reac-
tivity of allyl ketones with free ,,-positions (R2 = R3 = H,
Scheme 1). However, as far as we know, the only report pre-
sented to date has been when an aldol-type product, pre-
pared from allyl ketone and ethyl glyoxalate in the presence
of lithium diisopropylamide, was subsequently treated with
methanesulfonyl chloride to form the corresponding diene
system.9
DOI: 10.1055/s-0039-1690003; Art ID: ss-2019-z0299-op
Abstract 2-Acylbuta-1,3-dienes have been synthesized regioselective-
ly from aromatic and heteroaromatic ,-unsaturated ketones (readily
accessible via base-catalyzed addition of ketones to acetylenes) and al-
dehydes. The reaction smoothly proceeds with piperidine (10
mol%)/acetic acid (10 mol%) catalytic pair in boiling toluene to provide
synthetically attractive polyconjugated electron-deficient dienes in up
to 94% yield.
Key words condensation, C–C bond formation, unsaturated ketones,
aldehydes, conjugated dienes
The search for straightforward and efficient methods of
carbon–carbon bond formation, especially those based on
the principles of pot-atom-step-economy (PASE para-
digm),1 is among the main challenges of modern organic
chemistry. In this context, the base-catalyzed addition of
ketones to alkynes to afford ,-unsaturated ketones has re-
cently been discovered (Scheme 1).2 Due to inexpensive
starting materials and easy-to-handle catalytic systems (al-
kali metal hydroxides or alkoxides in DMSO), this exclusive-
ly E-stereoselective reaction has rapidly become an indis-
pensable tool for the synthesis of a broad range of carbo-
and heterocycles.3
Encouraged by this fact, we have initiated developing a
regio- and/or stereoselective approach to synthetically at-
tractive polyconjugated electron-deficient dienes in which
for the first time the condensation of now readily available
,-unsaturated ketones as active methylene compounds
with aldehydes was utilized (Scheme 2).
O
R2
R1
O
R3
and/or
O
R2
R3
+
R1
H
O
R2
R3
R1
O
O
MOR/DMSO
R2
R3
R3
+
R1
R1
100 °C, 30–60 min
Scheme 2 Possible products of the reaction between ,-unsaturated
ketones and aldehydes
R2
R1, R2 = H, Alk, c-Alk, Ar, HetAr; R3 = Ar, HetAr;
M = Na, K, Cs; R = H, t-Bu
We envisioned that acidity of methylene group in the -
position of ,-unsaturated ketones should be high enough
to ensure deprotonation under the action of a weak organic
base, for example, an amine. Indeed, when a mixture of
(E)-1,4-diphenyl-3-buten-1-one (1a), 4-nitrobenzaldehyde
Scheme 1 Base-catalyzed addition of ketones to alkynes
© 2019. Thieme. All rights reserved. — Synthesis 2019, 51, A–I
Georg Thieme Verlag KG, Rüdigerstraße 14, 70469 Stuttgart, Germany

B
D. A. Shabalin et al.
Paper
Synthesis
(2a), and piperidine (10 mol%) was refluxed in toluene for 3
hours, that is under Knoevenagel condensation condi-
tions,10 we observed formation of the desired diene 3aa (Ta-
ble 1, entry 3). The condensation reaction turned out to be
-regioselective but afforded a mixture of E- and Z-isomers
relative to newly formed C=C bond, while the existing C=C
bond of ketone 1a remained in the E-configuration.
Given that acidic additives facilitate the Knoevenagel
condensation by increasing the electrophilicity of the alde-
hyde group,10 we easily achieved full conversion of the
starting aldehyde 2a by the introduction of acetic acid (10
mol%, Table 1, entry 4) in the reaction mixture. Another is-
sue to be addressed was stereoselectivity of the reaction.
Although changing the catalyst and additive loadings (en-
tries 1–14) and nature (entries 15–23) had an impact on
E/Z-stereoselectivity of the model reaction, we finally failed
to carry out this condensation in a stereoselective mode.
Since it is well known that the stereoselectivity of the con-
densation reactions is governed by steric effects10 and, if
necessary, the E- and Z-isomers could be separated (see be-
Table 1 Condensation of ,-Unsaturated Ketone 1a with 4-Nitrobenzaldehyde (2a)a
O
Ph
O
O
Ph
Ph
Ph
Ph
Ph
1a
Catalyst (X mol%)
Additive (X mol%)
+
+
PhMe, 110–115 °C
O
H
NO2
O2N
O2N
(E,E)-3aa
(Z,E)-3aa
2a
Entry
Catalyst (mol%)
Additive (mol%)
Time (h)
Ratio of 2a/(E,E)-3aa/(Z,E)-3aab
1
–
–
3
3
3
3
3
3
3
1.5
6
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
100:0:0
100:0:0
40:32:28
0:55:45
0:50:50
0:65:35
15:73:12
29:57:14
0:55:45
50:43:7
10:75:15
0:35:65
0:35:65
0:35:65
3:73:24
47:40:13
68:22:10
2
–
AcOH (10)
–
3
piperidine (10)
piperidine (10)
piperidine (10)
piperidine (10)
piperidine (10)
piperidine (10)
piperidine (10)
piperidine (1)
piperidine (5)
piperidine (50)
piperidine (50)
piperidine (100)
pyrrolidine (10)
4
AcOH (10)
AcOH (50)
AcOH (100)
AcOH (200)
AcOH (100)
AcOH (100)
AcOH (100)
AcOH (100)
AcOH (10)
AcOH (50)
AcOH (10)
AcOH (100)
AcOH (100)
AcOH (100)
AcOH (100)
AcOH (100)
AcOH (100)
AcOH (100)
AcOH (100)
TFA (100)
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
morpholine (10)
PhCH2NH2 (10)
PhNH2 (10)
c
–
-alanine (10)
72:22:6
71:21:8
100:0:0
88:6:6
-aminocaproic acid (10)
L-proline (10)
t-BuOK (10)
piperidine (10)
piperidine (10)
piperidine (10)
65:32:3
100:0:0c
50:44:6
TsOH·H2O (100)
HCO2H (100)
a Reaction conditions: ketone 1a (0.6 mmol), aldehyde 2a (0.5 mmol), toluene (2 mL), 110–115 °С (oil bath).
b According to 1H NMR spectra of crude.
c Intensive tar formation.
© 2019. Thieme. All rights reserved. — Synthesis 2019, 51, A–I

C
D. A. Shabalin et al.
Paper
Synthesis
low), we have turned our attention to the examination of
the reaction tolerance toward a set of ,-unsaturated ke-
tones 1 and aldehydes 2 (Table 2).
115 °С] lead in both cases to the equilibrium mixture of iso-
mers in the ratio of E/Z = 35:65, that is identical to the one
obtained in the condensation of ,-unsaturated ketone 1d
and aldehyde 2a (Table 2).
As follows from Table 2, most of the ,-unsaturated ke-
tones 1 readily react with 4-nitrobenzaldehyde 2a, provid-
ing the condensation products as a mixture of isomers in
62–94% total yields. The presence of electron-donating
groups at the carbonyl function of ketones 1 impedes the
reaction; thus, the yield of diene 3ea (derived from 4-me-
thoxyphenyl-substituted ,-unsaturated ketone 1e) was
only 64% (in comparison with 88% yield of 3aa), while tert-
butyl-substituted ketone 1h gave even no traces of the de-
sired product 3ha after 8 hours (1H NMR).
As mentioned above, the E- and Z-isomers can be sepa-
rated that was exemplified by isolation of E- and Z-isomers
of diene 3da in a pure state in 23% and 59% yield, respec-
tively (Scheme 3). Heating of pure samples of E- and Z-iso-
mers of 3da under the condensation reaction conditions
[piperidine (10 mol%), acetic acid (10 mol%), toluene, 110–
Due to the lower electrophilicity of the starting alde-
hydes 2b–h compared to 4-nitrobenzaldehyde (2a), con-
densation of aromatic and heteroaromatic aldehydes 2b–g
with model ,-unsaturated ketone 1a was less effective,
and cyclohexanecarboxaldehyde (2h), a representative of
alkyl aldehydes, was completely inert in the studied reac-
tion. It should be noted that in all cases the starting ketone
1a was entirely consumed, while aldehydes 2 were still de-
tected in the crude (1H NMR), that indicates the tendency of
,-unsaturated ketones 1 to participate in diverse side re-
actions (e.g., base-catalyzed autocondensation followed by
a cascade formation of terphenyls).11
Unfortunately, all attempts to prepare diene 3aa in a
one-pot manner, starting from acetophenone and phenyl-
acetylene with the subsequent trapping of the enolate in-
Table 2 Substrate Scope of the Condensation of ,-Unsaturated Ketones 1 with Aldehydes 2a,b,c,d
Piperidine (10 mol%)
AcOH (10 mol%)
O
O
O
R2
R3
+
R2
R1
R1
PhMe, 110–115 °C
H
R3
1
2
3
O
O
O
O
O
Ph
Ph
Ph
Ph
Ph
Ph
Cl
Ph
F
MeO
NO2
NO2
NO2
NO2
NO2
3aa: 88% (E/Z = 55:45)
3ba: 79% (E/Z = 40:60)
3ca: 82% (E/Z = 50:50)
3da: 82% (E/Z = 35:65)
3ea: 64% (E/Z = 40:60)
Ph
O
O
O
O
O
Ph
Ph
Ph
Ph
F
Ph
S
NO2
NO2
NO2
NO2
NO2
3fa: 82% (E/Z = 50:50)
3ga: 91% (E/Z = 35:65)
3ha: no reaction
3ia: 94% (E/Z = 50:50)
3ja: 92% (E/Z = 30:70)
O
O
O
O
S
O
Ph
Ph
Ph
Ph
Ph
Ph
OMe
Ph
Ph
Ph
NO2
3la: 62% (E/Z = 50:50)
O
NMe2
Cl
3ac: 74% (E/Z = 50:50)
O
NO2
3ka: 87% (E/Z = 35:65)
3ab: 53% (E/Z = 70:30)
3ad: 19%e
O
O
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
N
HN
O
3ae: traces
3af: 31%e
3ag: 65% (E/Z = 65:35)
3ah: no reaction
a Reaction conditions: ketone 1 (0.6 mmol), aldehyde 2 (0.5 mmol), piperidine (5 L, 10 mol%), AcOH (3 L, 10 mol%), toluene (2 mL), 110–115 °С (oil bath).
b Isolated yields after column chromatography (silica gel, eluent hexane/Et2O, with gradient from 9:1 to 0:1).
c Reaction time was 3 h for 3aa, 3ba, 3ca, 3ja, 3ka, 3ab, 3ac, 3ad, 3ae, 3af, 4 h for 3ga, 3ia, 3la, 3ag, 5 h for 3da, 3ea, 3fa, and 8 h for 3ha, 3ah.
d Ratios of isomers were determined by 1H NMR spectra of the crude.
e Stereochemistry was not determined due to intensive tar formation.
© 2019. Thieme. All rights reserved. — Synthesis 2019, 51, A–I

D
D. A. Shabalin et al.
Paper
Synthesis
O
O
O
Piperidine (10 mol%)
AcOH (10 mol%)
Ph
Ph
Ph
O
H
Cl
+
O2N
+
Cl
PhMe
110–115 °C, 5 h
Cl
NO2
O2N
1d
2a
(E,E)-3da (23%)
(Z,E)-3da (59%)
Scheme 3 Condensation of ,-unsaturated ketone 1d with 4-nitrobenzaldehyde (2a)
termediate with 4-nitrobenzaldehyde (2a) (similar to the
recently reported alkylation of ,-unsaturated ketones)12
were unsuccessful. This is apparently caused by solvent ef-
fects since the first stage requires the use of DMSO as a sol-
vent, while the condensation reaction in DMSO under stan-
dard conditions (Table 1, entry 4) turned out to be ineffec-
tive.
The structures of all synthesized dienes 3, including the
configurational assignment and the location of the substit-
uents, were unambiguously proven by 1H, 13C, and 2D (NO-
ESY, 1H-13C HSQC, 1H-13C HMBC) NMR spectroscopy. For ex-
ample, in the 2D NOESY spectra of 3aa (Figure 1), cross-
peaks were observed between the signals of proton at the
C1′ and protons at the ortho-position of the benzoyl moiety
for E,E-isomer of 3aa, while for Z,E-isomer of 3aa cross-
peaks between the signals of proton at the C1′ and protons
at the C3 and C4 were detected. The cross-peaks between
the signals of olefinic protons at the C3 and C4 and protons
ylbutadienes are based on the reactions of lithium-,17 zinc-18
or tin-organic19 substrates with carboxylic acid derivatives
and rhodium-catalyzed carbonylative arylation of allenols
with arylboronic acids.20 Therefore, a successful employ-
ment of readily available ,-unsaturated ketones (adducts
of ketones with alkynes)2 as active methylene compounds
in the condensation with aldehydes contributes consider-
ably to the accessibility of synthetically attractive 2-acylbu-
tadienes.
In summary, we have successfully implemented the
condensation of ,-unsaturated ketones with aldehydes,
which proved to be an effective regioselective approach to
polyconjugated electron-deficient dienes (2-acylbuta-
dienes) based on the use of simple and cheap starting mate-
rials and catalytic system. Taking into account the rich
chemistry of dienes,21 here synthesized butadienes, addi-
tionally activated by the presence of an electron-withdraw-
ing acyl group, represent promising reactive reagents for
further synthetic applications.
at the ortho-position of phenyl moiety of 3aa and the values
3
of vicinal JH-3 H-4
,
(ca. 16 Hz) corresponds to the E-configu-
ration of C3–C4 double bond. Additionally, the configuration
of C1′–C2 double bond was confirmed by the values of vici-
All chemicals and solvents were purchased from commercial sources.
Toluene and piperidine were distilled over Na, and AcOH was distilled
with Ac2O in order to remove any H2O. Starting ,-unsaturated ke-
tones 1 were prepared according to the literature method.2 TLC was
carried out on Merck silica gel 60 F254 pre-coated aluminum foil
sheets and were visualized by UV light (254 nm). Column chromatog-
raphy was carried out using slurry packed Sigma Aldrich silica gel
(SiO2), 70–230 mesh, pore size 60 Å. NMR spectra were recorded from
solutions in CDCl3 on Bruker DPX-400 and AV-400 spectrometers
(400.1 MHz for 1H and 100.6 MHz for 13C). Chemical shifts () are
quoted in parts per million (ppm). The residual solvent peak, H 7.26
and C 77.10 was used as a reference. Coupling constants (J) are re-
ported in hertz (Hz). Standard abbreviations are used for denoting
multiplicity. Signals were assigned through analysis of 2D COSY, NO-
ESY, HMBC, and HSQC experiments if required. High-resolution mass
spectra were recorded from MeCN solution with 0.1% HFBA on HPLC
Agilent 1200/Agilent 6210 TOF instrument equipped with an electro-
spray ionization (ESI) source. Melting points (uncorrected) were mea-
sured on a digital melting point apparatus Electrothermal IA 9200.
nal 3JC-1 H-1′
equal to 6.7 Hz and 10.3 Hz for E,E- and Z,E-iso-
,
mers of 3aa, respectively.
H
H
H
O
H
O
4
3
H
1
3
2
4
2
1
H
H
H
H
H
1'
H
1'
H
H
H
H
H
NO2
NO2
(E,E)-3aa
(Z,E)-3aa
Figure 1 Cross-peaks in the NOESY (solid lines) and HMBC (dashed
lines) spectra of diene 3aa
It is relevant to note here that 2-acylbutadienes are less
accessible compounds in comparison with well-explored 1-
acylbutadienes.13 The first synthesis of a simple 2-acylbuta-
diene, namely 4-methyl-3-methylenepent-4-en-2-one, was
reported in 1962.14 Later studies revealed a low stability of
simple 2-acylbutadienes and their tendency to undergo a
spontaneous dimerization,15 which in some cases was re-
duced by trapping of dienes with carbonyliron complexes.16
Several known approaches to more stable substituted 2-ac-
Synthesis of New Starting ,-Unsaturated Ketones 1; General Pro-
cedure
A mixture of ketone (4.0 mmol), acetylene (4.0 mmol), and t-BuOK
(449 mg, 4.0 mmol) in DMSO (10 mL) was stirred at 100 °C for 30 min.
The reaction mixture after cooling to r.t. was diluted with H2O (10
mL), neutralized with aq NH4Cl, and extracted with Et2O (4 × 10 mL).
The combined organic extracts were washed with H2O (3 × 5 mL) and
© 2019. Thieme. All rights reserved. — Synthesis 2019, 51, A–I

E
D. A. Shabalin et al.
Paper
Synthesis
dried (MgSO4). After removal of the solvent, the residue was purified
by column chromatography (silica gel, eluent: hexane/Et2O with gra-
dient from 1:0 to 0:1) to afford the desired ,-unsaturated ketone 1.
HRMS (ESI-TOF): m/z calcd for [C16H13FO + H]+: 241.1029; found:
241.1022.
(E)-4-(3-Methoxyphenyl)-1-phenylbut-3-en-1-one (1k)
(E)-1-(4-Chlorophenyl)-4-phenylbut-3-en-1-one (1d)
Following the general procedure, 1k was prepared from acetophe-
none (480 mg, 4.0 mmol) and 3-methoxyphenylacetylene (529 mg,
4.0 mmol); white solid; yield: 360 mg (36%); mp 83–85 °C.
Following the general procedure, 1d was prepared from 4-chloroace-
tophenone (618 mg, 4.0 mmol) and phenylacetylene (408 mg, 4.0
mmol); white solid; yield: 360 mg (35%); mp 122–124 °C.
1H NMR (400.1 MHz, CDCl3):  = 7.95 (d, J = 8.6 Hz, 2 H, ArH), 7.46 (d,
J = 8.6 Hz, 2 H, ArH), 7.39–7.37 (m, 2 H, C6H5), 7.33–7.29 (m, 2 H,
C6H5), 7.25–7.21 (m, 1 H, C6H5), 6.57–6.41 (m, 2 H, CH=CH), 3.89–3.88
(m, 2 H, CH2).
1H NMR (400.1 MHz, CDCl3):  = 8.02–8.00 (m, 2 H, C6H5), 7.61–7.56
(m, 1 H, C6H5), 7.51–7.47 (m, 2 H, C6H5), 7.24–7.20 (m, 1 H, ArH),
6.99–6.97 (m, 1 H, ArH), 6.93–6.92 (m, 1 H, ArH), 6.80–6.77 (m, 1 H,
3
3
3
ArH), 6.53 (d, J = 16.1 Hz, 1 H, CH=CH), 6.48 (dt, J = 5.5 Hz, J = 16.1
Hz, 1 H, CH=CH), 3.92 (d, 3J = 5.5 Hz, 2 H, CH2), 3.81 (s, 3 H, OCH3).
13C{1H} NMR (100.6 MHz, CDCl3):  = 196.8, 139.8, 136.9, 135.0, 133.9,
13C{1H} NMR (100.6 MHz, CDCl3):  = 198.0, 159.8, 138.5, 136.6, 133.5,
129.8, 129.1, 128.6, 127.7, 126.4, 122.2, 42.8.
133.3, 129.6, 128.7, 128.4, 123.0, 119.1, 113.3, 111.5, 55.3, 42.7.
HRMS (ESI-TOF): m/z calcd for [C16H13ClO + H]+: 257.0733; found:
HRMS (ESI-TOF): m/z calcd for [C17H16O2 + H]+ 253.1229; found:
257.0767.
253.1235.
(E)-1-(4-Methoxyphenyl)-4-phenylbut-3-en-1-one (1e)
(E)-1-Phenyl-4-(thiophen-3-yl)but-3-en-1-one (1l)
Following the general procedure, 1e was prepared from 4-methoxy-
acetophenone (600 mg, 4.0 mmol) and phenylacetylene (408 mg, 4.0
mmol); white solid; yield: 425 mg (42%); mp 96–97 °C.
Following the general procedure, 1l was prepared from acetophenone
(480 mg, 4.0 mmol) and 3-ethynylthiophene (432 mg, 4.0 mmol);
white solid; yield: 384 mg (42%); mp 97–99 °C.
1H NMR (400.1 MHz, CDCl3):  = 7.92 (d, J = 8.2 Hz, 2 H, ArH), 7.40–
7.38 (m, 2 H, C6H5), 7.32–7.26 (m, 2 H, C6H5, 2 H, ArH), 7.24–7.20 (m, 1
H, C6H5), 6.57–6.44 (m, 2 H, CH=CH), 3.90–3.88 (m, 2 H, CH2), 2.42 (s,
3 H, OCH3).
1H NMR (400.1 MHz, CDCl3):  = 8.01–7.99 (m, 2 H, C6H5), 7.60–7.56
(m, 1 H, C6H5), 7.50–7.46 (m, 2 H, C6H5), 7.26–7.22 (m, 2 H, thienyl),
7.13 (s, 1 H, thienyl), 6.57 (d, 3J = 16.4 Hz, 1 H, CH=CH), 6.32 (dt,
3J = 6.9, 16.4 Hz, 1 H, CH=CH), 3.88 (d, 3J = 6.9 Hz, 2 H, CH2).
13C{1H} NMR (100.6 MHz, CDCl3):  = 197.7, 144.1, 137.1, 134.3, 133.5,
13C{1H} NMR (100.6 MHz, CDCl3):  = 198.0, 139.7, 136.8, 133.3, 128.8,
129.4, 128.6, 128.5, 127.5, 126.4, 122.9, 42.7, 21.7.
128.4, 127.9, 126.0, 125.1, 122.5, 121.8, 42.7.
HRMS (ESI-TOF): m/z calcd for [C17H16O2 + H]+: 253.1229; found:
HRMS (ESI-TOF): m/z calcd for [C14H12OS + H]+: 229.0687; found:
253.1245.
229.0686.
(E)-4-([1,1′-Biphenyl]-4-yl)-1-phenylbut-3-en-1-one (1i)
2-Acylbuta-1,3-dienes 3; General Procedure
Following the general procedure, 1i was prepared from acetophenone
(480 mg, 4.0 mmol) and 4-ethynyl-1,1′-biphenyl (713 mg, 4.0 mmol);
white solid; yield: 480 mg (40%); mp 147–149 °C.
1H NMR (400.1 MHz, CDCl3):  = 8.04–8.02 (m, 2 H, C6H5), 7.61–7.55
(m, 5 H, C6H5), 7.52–7.42 (m, 6 H, C6H5), 7.36–7.32 (m, 1 H, ArH),
6.62–6.49 (m, 2 H, CH=CH), 3.95–3.94 (m, 2 H, CH2).
A mixture of ketone 1 (0.6 mmol), aldehyde 2 (0.5 mmol), piperidine
(5 L, 0.05 mmol) and AcOH (3 L, 0.05 mmol) in toluene (2 mL) was
stirred at 110–115 °C (oil bath) for 3–8 h. After cooling to r.t., toluene
was removed under reduced pressure, and the residue was purified by
column chromatography (silica gel, eluent hexane/Et2O, with gradient
from 9:1 to 0:1) to afford the desired 2-acylbuta-1,3-diene 3.
13C{1H} NMR (100.6 MHz, CDCl3):  = 198.0, 140.8, 140.3, 136.7, 136.1,
133.3, 133.2, 128.9, 128.8, 128.4, 127.4, 127.3, 127.0, 126.8, 122.8,
42.8.
HRMS (ESI-TOF): m/z calcd for [C22H18O + H]+: 299.1436; found:
299.1454.
(3E)-2-(4-Nitrobenzylidene)-1,4-diphenylbut-3-en-1-one (3aa)
Following the general procedure, 3aa was prepared from (E)-1,4-di-
phenylbut-3-en-1-one (1a; 133 mg, 0.6 mmol) and 4-nitrobenzalde-
hyde (2a; 76 mg, 0.5 mmol); yellow solid; yield: 157 mg (88%);
E:Z = 55:45.
1H NMR (400.1 MHz, CDCl3):  (E-isomer) = 8.30 (d, J = 8.7 Hz, 2 H,
ArH), 8.03–8.01 (m, 2 H, C6H5), 7.62 (d, J = 8.7 Hz, 2 H, ArH), 7.57–7.26
(m, 8 H, C6H5), 7.24 (d, J = 16.5 Hz, 1 H, CH=CH), 6.82 (d, J = 16.5 Hz, 1
H, CH=CH), 6.76 (s, 1 H, CH=);  (Z-isomer) = 8.03–8.01 (m, 2 H, C6H5,
2 H, ArH), 7.57–7.26 (m, 10 H, C6H5), 7.08 (d, J = 16.5 Hz, 1 H, CH=CH),
6.90 (s, 1 H, CH=), 6.47 (d, J = 16.5 Hz, 1 H, CH=CH).
13C{1H} NMR (100.6 MHz, CDCl3):  (E-isomer) = 197.0, 147.0, 142.1,
142.1, 137.0, 136.5, 136.2, 133.7, 130.3, 130.1, 130.1, 128.7, 128.7,
128.7, 126.9, 123.8, 121.5;  (Z-isomer) = 198.6, 146.7, 144.0, 141.7,
136.2, 135.5, 134.7, 134.6, 129.5, 129.2, 129.1, 129.1, 128.8, 128.8,
128.5, 126.9, 123.8.
(E)-4-(3-Fluorophenyl)-1-phenylbut-3-en-1-one (1j)
Following the general procedure, 1j was prepared from acetophenone
(480 mg, 4.0 mmol) and 3-fluorophenylacetylene (480 mg, 4.0
mmol); white solid; yield: 384 mg (40%); mp 94–96 °C.
1H NMR (400.1 MHz, CDCl3):  = 8.02–7.99 (m, 2 H, C6H5), 7.61–7.57
(m, 1 H, C6H5), 7.51–7.47 (m, 2 H, C6H5), 7.29–7.23 (m, 1 H, ArH),
7.16–7.14 (m, 1 H, ArH), 7.11–7.07 (m, 1 H, ArH), 6.94–6.89 (m, 1 H,
ArH), 6.52–6.50 (m, 2 H, CH=CH), 3.93–3.92 (m, 2 H, CH2).
13C{1H} NMR (100.6 MHz, CDCl3):  = 197.7, 163.1 (J = 245.1 Hz),
139.4 (J = 7.7 Hz), 136.5, 133.4, 132.5 (J = 2.5 Hz), 130.0 (J = 8.4 Hz),
128.8, 128.3, 124.1, 122.2 (J = 2.7 Hz), 114.3 (J = 21.4 Hz), 112.8
(J = 21.8 Hz), 42.5.
HRMS (ESI-TOF): m/z calcd for [C23H17NO3 + H]+: 356.1286; found:
356.1315.
© 2019. Thieme. All rights reserved. — Synthesis 2019, 51, A–I

F
D. A. Shabalin et al.
Paper
Synthesis
(3E)-1-([1,1′-Biphenyl]-4-yl)-2-(4-nitrobenzylidene)-4-phenylbut-
3-en-1-one (3ba)
H, CH=CH), 6.78 (d, J = 17.0 Hz, 1 H, CH=CH), 6.76 (s, 1 H, CH=);  (Z-
isomer) = 8.04 (d, J = 8.8 Hz, 2 H, ArH), 7.95 (d, J = 8.4 Hz, 2 H, ArH),
7.41–7.27 (m, 9 H, ArH, C6H5), 7.07 (d, J = 16.4 Hz, 1 H, CH=CH), 6.90
(s, 1 H, CH=), 6.44 (d, J = 16.4 Hz, 1 H, CH=CH).
13C{1H} NMR (100.6 MHz, CDCl3):  (E-isomer) = 195.9, 147.3, 142.1,
142.0, 140.3, 137.3, 136.1, 134.9, 131.6, 130.5, 130.4, 129.1, 129.0,
128.9, 127.0, 123.9, 121.3;  (Z-isomer) = 197.4, 147.0, 143.6, 141.6,
141.3, 136.1, 134.9, 133.9, 130.9, 129.6, 129.3, 129.2, 128.9, 128.9,
128.2, 126.9, 124.0.
Following the general procedure, 3ba was prepared from (E)-1-([1,1′-
biphenyl]-4-yl)-4-phenylbut-3-en-1-one (1b; 179 mg, 0.6 mmol) and
4-nitrobenzaldehyde (2a; 76 mg, 0.5 mmol); yellow solid; yield: 170
mg (79%); E/Z = 40:60.
1H NMR (400.1 MHz, CDCl3):  (E-isomer) = 8.31 (d, J = 8.6 Hz, 2 H,
ArH), 8.11–8.03 (m, 2 H, ArH), 7.73 (d, J = 8.6 Hz, 2 H, ArH), 7.66–7.64
(m, 1 H, ArH), 7.50–7.26 (m, 11 H, C6H5, 1 H, CH=CH), 6.85 (d, J = 16.4
Hz, 1 H, CH=CH), 6.79 (s, 1 H, CH=);  (Z-isomer) = 8.11–8.03 (m, 4 H,
ArH), 7.66–7.64 (m, 3 H, ArH), 7.59–7.58 (m, 2 H, ArH), 7.50–7.26 (m,
9 H, ArH), 7.11 (d, J = 16.4 Hz, 1 H, CH=CH), 6.92 (s, 1 H, CH=), 6.50 (d,
J = 16.4 Hz, 1 H, CH=CH).
HRMS (ESI-TOF): m/z calcd for [C23H16ClNO3 + H]+: 390.0897; found:
390.0932.
(3E)-1-(4-Methoxyphenyl)-2-(4-nitrobenzylidene)-4-phenylbut-
3-en-1-one (3ea)
13C{1H} NMR (100.6 MHz, CDCl3):  (E-isomer) = 196.7, 147.1, 146.4,
142.3, 142.2, 139.6, 137.0, 136.2, 135.1, 129.3, 129.1, 129.0, 128.8,
Following the general procedure, 3ea was prepared from (E)-1-(4-
methoxyphenyl)-4-phenylbut-3-en-1-one (1e; 151 mg, 0.6 mmol)
and 4-nitrobenzaldehyde (2a; 76 mg, 0.5 mmol); yellow solid; yield:
123 mg (64%); E/Z = 40:60.
1H NMR (400.1 MHz, CDCl3):  (E-isomer) = 8.29 (d, J = 8.6 Hz, 2 H,
ArH), 7.92 (d, J = 8.0 Hz, 2 H, ArH), 7.62 (d, J = 8.6 Hz, 2 H, ArH), 7.33–
7.26 (m, 5 H, C6H5, 2 H, ArH), 7.24 (d, J = 16.4 Hz, 1 H, CH=CH), 6.80 (d,
J = 16.7 Hz, 1 H, CH=CH), 6.73 (s, 1 H, CH=), 2.44 (s, 3 H, OCH3);  (Z-
isomer) = 8.01 (d, J = 8.8 Hz, 2 H, ArH), 7.92 (d, J = 8.2 Hz, 2 H, ArH),
7.39–7.37 (m, 2 H, ArH, 2 H, C6H5), 7.33–7.22 (m, 2 H, ArH, 3 H, C6H5),
7.08 (d, J = 16.4 Hz, 1 H, CH=CH), 6.87 (s, 1 H, CH=), 6.47 (d, J = 16.4
Hz, 1 H, CH=CH), 2.38 (s, 3 H, OCH3).
13C{1H} NMR (100.6 MHz, CDCl3):  (E-isomer) = 196.9, 147.2, 144.9,
142.7, 142.5, 137.1, 136.4, 134.0, 130.4, 130.4, 129.8, 129.5, 128.9,
128.8, 127.0, 123.9, 121.7, 21.9;  (Z-isomer) = 198.2, 146.7, 145.8,
144.3, 141.9, 136.3, 134.7, 133.2, 129.9, 129.7, 129.2, 128.8, 128.8,
128.7, 128.6, 126.9, 123.8, 21.9.
128.8, 128.7, 128.7, 128.5, 127.3, 127.3, 127.0, 121.5;
 (Z-
isomer) = 198.2, 147.2, 146.6, 144.0, 141.7, 139.4, 136.1, 134.6, 134.1,
130.8, 130.4, 130.1, 129.2, 129.0, 129.0, 128.8, 128.5, 127.7, 127.3,
126.8, 123.8.
HRMS (ESI-TOF): m/z calcd for [C29H21NO3 + H]+: 432.1600; found:
432.1603.
(3E)-1-(4-Fluorophenyl)-2-(4-nitrobenzylidene)-4-phenylbut-3-
en-1-one (3ca)
Following the general procedure, 3ca was prepared from (E)-1-(4-flu-
orophenyl)-4-phenylbut-3-en-1-one (1c; 144 mg, 0.6 mmol) and 4-
nitrobenzaldehyde (2a; 76 mg, 0.5 mmol); yellow solid; yield: 154 mg
(82%); E/Z = 50:50.
1H NMR (400.1 MHz, CDCl3):  (E-isomer) = 8.30 (d, J = 8.8 Hz, 2 H,
ArH), 8.07–8.03 (m, 2 H, ArH), 7.62 (d, J = 8.8 Hz, 2 H, ArH), 7.35–7.28
(m, 5 H, C6H5), 7.20 (d, J = 16.7 Hz, 1 H, CH=CH), 7.20–7.16 (m, 2 H,
ArH), 6.78 (d, J = 16.7 Hz, 1 H, CH=CH), 6.75 (s, 1 H, CH=);  (Z-
isomer) = 8.06–8.02 (m, 4 H, ArH), 7.39–7.27 (m, 7 H, ArH, C6H5),
7.12–7.08 (m, 2 H, ArH), 7.07 (d, J = 16.4 Hz, 1 H, CH=CH), 6.90 (s, 1 H,
CH=), 6.45 (d, J = 16.4 Hz, 1 H, CH=CH).
HRMS (ESI-TOF): m/z calcd for [C24H19NO4 + H]+: 386.1392; found:
386.1406.
(3E)-1-(Naphthalen-2-yl)-2-(4-nitrobenzylidene)-4-phenylbut-3-
13C{1H} NMR (100.6 MHz, CDCl3):  (E-isomer) = 195.7, 166.2 (d,
J = 256.5 Hz), 147.3, 142.2, 142.2, 137.3, 136.2, 132.9 (d, J = 9.5 Hz),
132.9 (d, J = 3.0 Hz), 130.4, 130.1, 129.0, 128.9, 127.0, 124.0, 121.4,
116.1 (d, J = 22.1 Hz);  (Z-isomer) = 197.1, 166.6 (d, J = 257.7 Hz),
146.8, 143.7, 141.6, 136.1, 134.7, 132.3 (d, J = 9.7 Hz), 132.0 (d, J = 2.8
Hz), 129.2, 129.1, 128.9, 128.8, 128.3, 126.9, 123.9, 116.5 (d, J = 22.1
Hz).
en-1-one (3fa)
Following the general procedure, 3fa was prepared from (E)-1-(naph-
thalen-2-yl)-4-phenylbut-3-en-1-one (1f; 163 mg, 0.6 mmol) and 4-
nitrobenzaldehyde (2a; 76 mg, 0.5 mmol); yellow solid; yield: 166 mg
(82%); E/Z = 50:50.
1H NMR (400.1 MHz, CDCl3):  (E-isomer) = 8.50 (s, 1 H, naphthyl),
8.32 (d, J = 8.6 Hz, 2 H, ArH), 8.14–8.09 (m, 1 H, naphthyl), 8.00–7.85
(m, 4 H, C6H5, naphthyl), 7.66 (d, J = 8.6 Hz, 2 H, ArH), 7.64–7.50 (m, 3
H, C6H5, naphthyl), 7.42–7.26 (m, 3 H, C6H5, naphthyl, 1 H, CH=CH),
HRMS (ESI-TOF): m/z calcd for [C23H16FNO3 + H]+: 374.1192; found:
374.1217.
6.86 (d, J = 16.4 Hz,
1 H, CH=CH), 6.82 (s, 1 H, CH=);  (Z-
(3E)-1-(4-Chlorophenyl)-2-(4-nitrobenzylidene)-4-phenylbut-3-
en-1-one (3da)
isomer) = 8.48 (s, 1 H, naphthyl), 8.14–8.09 (m, 1 H, naphthyl), 8.00–
7.85 (m, 5 H, ArH, C6H5, naphthyl), 7.64–7.50 (m, 2 H, C6H5, naphthyl),
7.42–7.26 (m, 7 H, C6H5, naphthyl), 7.16 (d, J = 16.4 Hz, 1 H, CH=CH),
6.96 (s, 1 H, CH=), 6.51 (d, J = 16.4 Hz, 1 H, CH=CH).
13C{1H} NMR (100.6 MHz, CDCl3):  (E-isomer) = 197.2, 147.3, 142.6,
142.4, 137.2, 136.3, 136.0, 133.9, 132.7, 132.5, 130.5, 130.3, 129.8,
129.3, 129.1, 128.9, 128.8, 128.0, 127.1, 127.1, 125.1, 124.0, 121.7; 
(Z-isomer) = 198.7, 146.8, 144.3, 141.8, 136.4, 136.2, 134.9, 133.0,
132.7, 132.5, 129.9, 129.4, 129.3, 129.3, 129.2, 128.8, 128.8, 128.7,
128.0, 127.1, 126.9, 124.0, 123.9.
Following the general procedure, 3da was prepared from (E)-1-(4-
chlorophenyl)-4-phenylbut-3-en-1-one (1d; 154 mg, 0.6 mmol) and
4-nitrobenzaldehyde (2a; 76 mg, 0.5 mmol). After toluene evapora-
tion, the residue was treated with cold Et2O (2 mL) to afford the pure
Z-isomer of 3da; yellow solid; yield: 115 mg (59%); mp 196–198 °C.
Et2O mother solution was evaporated, and the obtained residue was
purified by column chromatography (silica gel, eluent hexane/Et2O,
with gradient from 9:1 to 0:1) to give the pure E-isomer of 3da; yel-
low solid; yield: 44 mg (23%); mp 114–116 °C.
HRMS (ESI-TOF): m/z calcd for [C27H19NO3 + H]+: 406.1443; found:
406.1465.
1H NMR (400.1 MHz, CDCl3):  (E-isomer) = 8.29 (d, J = 8.8 Hz, 2 H,
ArH), 7.96 (d, J = 8.4 Hz, 2 H, ArH), 7.62 (d, J = 8.8 Hz, 2 H, ArH), 7.48
(d, J = 8.4 Hz, 2 H, ArH), 7.36–7.28 (m, 5 H, C6H5), 7.24 (d, J = 17.0 Hz, 1
© 2019. Thieme. All rights reserved. — Synthesis 2019, 51, A–I

G
D. A. Shabalin et al.
Paper
Synthesis
(3E)-2-(4-Nitrobenzylidene)-4-phenyl-1-(thiophen-2-yl)but-3-en-
1-one (3ga)
13C{1H} NMR (100.6 MHz, CDCl3):  (E-isomer) = 196.9, 163.1 (d,
J = 246.1 Hz), 147.3, 142.0, 141.7, 138.6 (d, J = 7.7 Hz), 136.4, 135.7 (d,
J = 2.7 Hz), 133.9, 131.4, 130.4, 130.3, 130.2, 129.7, 123.9, 122.9 (d,
J = 2.7 Hz), 122.7, 115.6 (d, J = 21.4 Hz), 113.3 (d, J = 21.9 Hz);  (Z-
isomer) = 198.4, 163.1 (d, J = 246.1 Hz), 146.8, 143.5, 141.5, 138.5 (d,
J = 7.7 Hz), 135.3, 134.7, 133.2 (d, J = 2.8 Hz), 130.4, 130.2, 130.0,
129.5, 129.3, 129.2, 128.8, 123.8, 115.5 (d, J = 21.4 Hz), 113.0 (d,
J = 22.0 Hz).
Following the general procedure, 3ga was prepared from (E)-4-phe-
nyl-1-(thiophen-2-yl)but-3-en-1-one (1g; 137 mg, 0.6 mmol) and 4-
nitrobenzaldehyde (2a; 76 mg, 0.5 mmol); yellow solid; yield: 164 mg
(91%); E/Z = 35:65.
1H NMR (400.1 MHz, CDCl3):  (E-isomer) = 8.29 (d, J = 8.8 Hz, 2 H,
ArH), 7.80–7.79 (m, 1 H, thienyl), 7.77–7.76 (m, 1 H, thienyl), 7.62 (d,
J = 8.8 Hz, 2 H, ArH), 7.46–7.27 (m, 5 H, C6H5), 7.20 (d, J = 16.4 Hz, 1 H,
CH=CH), 7.18–7.16 (m, 1 H, thienyl), 6.91 (d, J = 16.4 Hz, 1 H, CH=CH),
6.90 (s, 1 H, CH=);  (Z-isomer) = 8.05 (d, J = 8.8 Hz, 2 H, ArH), 7.70–
7.69 (m, 1 H, thienyl), 7.63–7.61 (m, 1 H, thienyl), 7.46–7.27 (m, 5 H,
C6H5, 2 H, ArH), 7.05 (d, J = 16.4 Hz, 1 H, CH=CH), 7.03–7.01 (m, 1 H,
thienyl), 6.97 (s, 1 H, CH=), 6.62 (d, J = 16.4 Hz, 1 H, CH=CH).
13C{1H} NMR (100.6 MHz, CDCl3):  (E-isomer) = 188.9, 147.3, 143.7,
142.2, 142.0, 137.1, 136.3, 135.6, 135.4, 130.4, 129.3, 128.9, 128.8,
128.5, 127.1, 123.9, 121.1;  (Z-isomer) = 190.3, 146.8, 143.8, 143.2,
141.7, 136.2, 136.2, 135.4, 134.6, 130.1, 129.1, 128.9, 128.8, 128.8,
126.9, 123.9, 128.1.
HRMS (ESI-TOF): m/z calcd for [C23H16FNO3 + H]+: 374.1192; found:
374.1216.
(3E)-4-(3-Methoxyphenyl)-2-(4-nitrobenzylidene)-1-phenylbut-
3-en-1-one (3ka)
Following the general procedure, 3ka was prepared from (E)-4-(3-
methoxyphenyl)-1-phenylbut-3-en-1-one (1k; 151 mg, 0.6 mmol)
and 4-nitrobenzaldehyde (2a; 76 mg, 0.5 mmol); yellow solid; yield:
167 mg (87%); E:Z = 35:65.
1H NMR (400.1 MHz, CDCl3):  (E-isomer) = 8.28 (d, J = 8.7 Hz, 2 H,
ArH), 8.03–7.98 (m, 2 H, C6H5), 7.61 (d, J = 8.7 Hz, 2 H, ArH), 7.59–7.55
(m, 1 H, C6H5), 7.52–7.41 (m, 2 H, C6H5), 7.24–7.20 (m, 1 H, ArH, 1 H,
CH=CH), 6.99–6.95 (m, 1 H, ArH), 6.90–6.80 (m, 2 H, ArH), 6.79 (d,
J = 16.4 Hz, 1 H, CH=CH), 6.76 (s, 1 H, CH=), 3.77 (s, 3 H, OCH3);  (Z-
isomer) = 8.03–7.98 (m, 2 H, C6H5, 2 H, ArH), 7.59–7.55 (m, 1 H, C6H5),
7.52–7.48 (m, 1 H, ArH), 7.45–7.41 (m, 2 H, C6H5), 7.36 (d, J = 8.8 Hz, 2
H, ArH), 7.26–7.20 (m, 1 H, ArH), 7.08 (d, J = 16.4 Hz, 1 H, CH=CH),
6.99–6.95 (m, 1 H, ArH), 6.90 (s, 1 H, CH=), 6.84–6.80 (m, 1 H, ArH),
6.43 (d, J = 16.4 Hz, 1 H, CH=CH), 3.79 (s, 3 H, OCH3).
13C{1H} NMR (100.6 MHz, CDCl3):  (E-isomer) = 197.13, 147.15,
146.67, 142.19, 142.16, 137.68, 136.97, 136.47, 133.79, 130.46,
129.80, 129.19, 129.19, 128.77, 123.88, 121.82, 119.42, 114.25,
112.62, 55.27;  (Z-isomer) = 198.65, 159.87, 143.91, 141.67, 137.55,
135.43, 134.59, 134.54, 130.39, 130.19, 129.74, 129.53, 129.22,
129.13, 128.75, 123.82, 119.47, 114.52, 111.99, 55.27.
HRMS (ESI-TOF): m/z calcd for [C21H15NO3S + H]+: 362.0851; found:
362.0855.
(3E)-4-([1,1′-Biphenyl]-4-yl)-2-(4-nitrobenzylidene)-1-phenylbut-
3-en-1-one (3ia)
Following the general procedure, 3ia was prepared from (E)-4-([1,1′-
biphenyl]-4-yl)-1-phenylbut-3-en-1-one (1i; 179 mg, 0.6 mmol) and
4-nitrobenzaldehyde (2a; 76 mg, 0.5 mmol); yellow solid; yield: 202
mg (94%); E/Z = 50:50.
1H NMR (400.1 MHz, CDCl3):  (E-isomer) = 8.31 (d, J = 8.7 Hz, 2 H,
ArH), 8.05–8.01 (m, 2 H, C6H5), 7.65–7.32 (m, 14 H, ArH), 7.30 (d,
J = 16.4 Hz, 1 H, CH=CH), 6.87 (d, J = 16.4 Hz, 1 H, CH=CH), 6.78 (s, 1 H,
CH=);  (Z-isomer) = 8.05–8.01 (m, 2 H, C6H5, 2 H, ArH), 7.65–7.32 (m,
14 H, C6H5), 7.13 (d, J = 16.4 Hz, 1 H, CH=CH), 6.92 (s, 1 H, CH=), 6.51
(d, J = 16.4 Hz, 1 H, CH=CH).
HRMS (ESI-TOF): m/z calcd for [C24H19NO4 + H]+: 386.1392; found:
386.1400.
13C{1H} NMR (100.6 MHz, CDCl3):  (E-isomer) = 197.2, 147.2, 142.4,
142.3, 141.7, 140.3, 136.7, 136.6, 135.3, 133.8, 130.4, 130.2, 129.3,
(3E)-2-(4-Nitrobenzylidene)-1-phenyl-4-(thiophen-3-yl)but-3-en-
1-one (3la)
129.2, 128.9, 128.9, 128.8, 127.2, 127.0, 124.0, 121.5;
 (Z-
isomer) = 198.7, 146.8, 144.1, 141.8, 141.5, 140.4, 135.6, 135.2, 134.6,
134.3, 130.3, 129.6, 129.1, 128.5, 127.7, 127.7, 127.5, 127.5, 127.4,
127.0, 123.9.
HRMS (ESI-TOF): m/z calcd for [C29H21NO3 + H]+: 432.1600; found:
Following the general procedure, 3la was prepared from (E)-1-phe-
nyl-4-(thiophen-3-yl)but-3-en-1-one (1l; 137 mg, 0.6 mmol) and 4-
nitrobenzaldehyde (2a; 76 mg, 0.5 mmol); yellow solid; yield: 112 mg
(62%); E/Z = 50:50.
432.1637.
1H NMR (400.1 MHz, CDCl3):  (E-isomer) = 8.29 (d, J = 8.7 Hz, 2 H,
ArH), 8.02–8.00 (m, 2 H, C6H5), 7.62–7.55 (m, 1 H, C6H5, 2 H, ArH),
7.53–7.49 (m, 2 H, C6H5), 7.31–7.26 (m, 2 H, thienyl), 7.21–7.19 (m, 1
H, thienyl), 7.08 (d, J = 16.4 Hz, 1 H, CH=CH), 6.83 (d, J = 16.4 Hz, 1 H,
CH=CH), 6.72 (s, 1 H, CH=);  (Z-isomer) = 8.02–8.00 (m, 2 H, C6H5, 2
H, ArH), 7.60–7.55 (m, 1 H, C6H5), 7.45–7.41 (m, 2 H, C6H5), 7.35 (d,
J = 8.8 Hz, 2 H, ArH), 7.31–7.26 (m, 2 H, thienyl), 7.21–7.19 (m, 1 H,
thienyl), 6.92 (d, J = 16.3 Hz, 1 H, CH=CH), 6.85 (s, 1 H, CH=), 6.47 (d,
J = 16.4 Hz, 1 H, CH=CH).
13C{1H} NMR (100.6 MHz, CDCl3):  (E-isomer) = 197.2, 147.2, 142.4,
142.4, 139.3, 136.6, 133.8, 131.2, 130.4, 130.2, 129.8, 129.2, 128.8,
126.8, 125.0, 124.0, 121.5;  (Z-isomer) = 198.7, 146.7, 144.2, 141.8,
139.2, 135.5, 134.6, 129.6, 129.6, 129.2, 129.2, 128.8, 128.5, 126.7,
124.7, 124.6, 123.9.
(3E)-4-(3-Fluorophenyl)-2-(4-nitrobenzylidene)-1-phenylbut-3-
en-1-one (3ja)
Following the general procedure, 3ja was prepared from (E)-4-(3-flu-
orophenyl)-1-phenylbut-3-en-1-one (1j; 144 mg, 0.6 mmol) and 4-
nitrobenzaldehyde (2a; 76 mg, 0.5 mmol); yellow solid; yield: 171 mg
(92%); E/Z = 30:70.
1H NMR (400.1 MHz, CDCl3):  (E-isomer) = 8.30 (d, J = 8.8 Hz, 2 H,
ArH), 8.02–7.99 (m, 2 H, C6H5), 7.65–7.56 (m, 4 H, ArH), 7.29–7.23 (m,
2 H, ArH), 7.22 (d, J = 16.4 Hz, 1 H, CH=CH), 7.12–7.02 (m, 2 H, ArH),
6.97–6.92 (m, 1 H, ArH), 6.81 (s, 1 H, CH=), 6.80 (d, J = 16.4 Hz, 1 H,
CH=CH);  (Z-isomer) = 8.02–7.99 (m, 2 H, C6H5, 2 H, ArH), 7.53–7.49
(m, 1 H, C6H5), 7.45–7.42 (m, 2 H, C6H5), 7.37 (d, J = 8.8 Hz, 2 H, ArH),
7.29–7.23 (m, 1 H, ArH), 7.12–7.02 (m, 2 H, ArH), 7.07 (d, J = 16.4 Hz, 1
H, CH=CH), 6.97–6.92 (m, 1 H, ArH), 6.92 (s, 1 H, CH=), 6.41 (d, J = 16.4
Hz, 1 H, CH=CH).
HRMS (ESI-TOF): m/z calcd for [C21H15NO3S + H]+: 362.0851; found:
362.0864.
© 2019. Thieme. All rights reserved. — Synthesis 2019, 51, A–I

H
D. A. Shabalin et al.
Paper
Synthesis
(3E)-2-Benzylidene-1,4-diphenylbut-3-en-1-one (3ab)
(3E)-2-[(1H-Pyrrol-2-yl)methylene]-1,4-diphenylbut-3-en-1-one
(3af)
Following the general procedure, 3ab was prepared from (E)-1,4-di-
phenylbut-3-en-1-one (1a; 133 mg, 0.6 mmol) and benzaldehyde
(2b; 53 mg, 0.5 mmol); yellow oil; yield: 82 mg (53%); E/Z = 70:30.
Following the general procedure, 3af was prepared from (E)-1,4-di-
phenylbut-3-en-1-one (1a; 133 mg, 0.6 mmol) and 1H-pyrrole-2-car-
baldehyde (2f; 48 mg, 0.5 mmol); orange oil; yield: 47 mg (31%); pre-
dominantly Z-isomer.
1H NMR (400.1 MHz, CDCl3):  (Z-isomer) = 9.26 (br s, 1 H, NH), 8.04–
8.03 (m, 2 H, C6H5), 7.59–7.55 (m, 1 H, C6H5), 7.47–7.44 (m, 2 H, C6H5),
7.29–7.26 (m, 4 H, C6H5), 7.22–7.18 (m, 1 H, C6H5), 7.00 (d, J = 16.3 Hz,
1 H, CH=CH), 6.86 (s, 1 H, CH=), 6.79–6.77 (m, 1 H, pyridyl), 6.41–6.38
(m, 1 H, pyridyl), 6.25 (d, J = 16.3 Hz, 1 H, CH=CH), 6.22–6.20 (m, 1 H,
pyridyl).
1H NMR (400.1 MHz, CDCl3):  (E-isomer) = 8.05–8.03 (m, 2 H, C6H5),
7.61–7.57 (m, 1 H, C6H5), 7.51–7.13 (m, 12 H, C6H5, 1 H, CH=CH), 6.88
(d, J = 16.4 Hz, 1 H, CH=CH), 6.86 (s, 1 H, CH=);  (Z-isomer) = 8.08–
8.06 (m, 2 H, C6H5), 7.51–7.13 (m, 13 H, C6H5), 7.09 (d, J = 16.4 Hz, 1 H,
CH=CH), 6.82 (s, 1 H, CH=), 6.39 (d, J = 16.4 Hz, 1 H, CH=CH).
13C{1H} NMR (100.6 MHz, CDCl3):  (E-isomer) = 198.0, 138.9, 137.3,
137.0, 135.6, 134.9, 134.7, 133.2, 130.2, 129.9, 128.8, 128.7, 128.6,
128.5, 128.5, 126.8, 122.8;  (Z-isomer) = 199.6, 140.0, 136.7, 135.9,
135.2, 134.0, 132.2, 131.9, 129.6, 129.3, 128.9, 128.6, 128.4, 128.2,
128.0, 128.0, 126.5.
13C{1H} NMR (100.6 MHz, CDCl3):  (Z-isomer) = 200.6, 137.2, 137.1,
133.8, 131.9, 130.1, 129.9, 129.6, 128.8, 128.8, 128.7, 127.6, 126.2,
124.9, 121.9, 115.8, 110.5.
HRMS (ESI-TOF): m/z calcd for [C23H18O + H]+: 311.1436; found:
311.1449.
HRMS (ESI-TOF): m/z calcd for [C21H17NO + H]+: 300.1388; found:
300.1421.
(3E)-2-(4-Chlorobenzylidene)-1,4-diphenylbut-3-en-1-one (3ac)
(3E)-2-(Furan-2-ylmethylene)-1,4-diphenylbut-3-en-1-one (3ag)
Following the general procedure, 3ac was prepared from (E)-1,4-di-
phenylbut-3-en-1-one (1a; 133 mg, 0.6 mmol) and 4-chlorobenzal-
dehyde (2c; 70 mg, 0.5 mmol); pale yellow solid; yield: 128 mg (74%);
E/Z = 50:50.
Following the general procedure, 3ag was prepared from (E)-1,4-di-
phenylbut-3-en-1-one (1a; 133 mg, 0.6 mmol) and furfural (2g; 48
mg, 0.5 mmol); brown oil; yield: 98 mg (65%); E/Z = 65:35.
1H NMR (400.1 MHz, CDCl3):  (E-isomer) = 8.03–7.99 (m, 2 H, Ph),
7.60–7.23 (m, 12 H, C6H5, 1 H, CH=CH), 6.80 (d, J = 16.2 Hz, 1 H,
CH=CH), 6.76 (s, 1 H, CH=);  (Z-isomer) = 8.03–7.99 (m, 2 H, C6H5),
7.60–7.23 (m, 8 H, C6H5), 7.17 (d, J = 8.7 Hz, 2 H, ArH), 7.13 (d, J = 8.7
Hz, 2 H, ArH), 7.05 (d, J = 16.4 Hz, 1 H, CH=CH), 6.82 (s, 1 H, CH=), 6.37
(d, J = 16.4 Hz, 1 H, CH=CH).
13C{1H} NMR (100.6 MHz, CDCl3):  (mixture of isomers) = 199.4,
197.8, 140.7, 139.6, 137.1, 136.8, 136.6, 135.8, 135.5, 134.4, 134.3,
134.1, 133.9, 133.8, 133.4, 133.0, 132.5, 131.1, 130.6, 130.2, 130.0,
129.6, 129.0, 128.9, 128.8, 128.8, 128.7, 128.6, 128.4, 128.2, 126.8,
126.6, 122.3.
1H NMR (400.1 MHz, CDCl3):  (E-isomer) = 7.97–7.95 (m, 2 H, C6H5),
7.91 (d, J = 16.5 Hz, 1 H, CH=CH), 7.63 (d, J = 1.8 Hz, 1 H, furyl), 7.59–
7.55 (m, 1 H, C6H5), 7.49–7.43 (m, 4 H, C6H5), 7.34–7.29 (m, 2 H, C6H5),
7.23–7.21 (m, 1 H, C6H5), 6.83 (d, J = 16.5 Hz, 1 H, CH=CH), 6.59 (d,
J = 3.4 Hz, 1 H, furyl), 6.53 (dd, J = 1.8, 3.4 Hz, 1 H, furyl), 6.50 (s, 1 H,
CH=);  (Z-isomer) = 8.07–8.06 (m, 2 H, C6H5), 7.59–7.55 (m, 1 H,
C6H5), 7.49–7.43 (m, 2 H, C6H5), 7.36–7.34 (m, 4 H, C6H5), 7.29–7.26
(m, 1 H, C6H5), 7.19 (d, J = 1.8 Hz, 1 H, furyl), 7.00 (d, J = 16.3 Hz, 1 H,
CH=CH), 6.64 (s, 1 H, CH=), 6.33 (d, J = 16.3 Hz, 1 H, CH=CH), 6.30 (d,
J = 3.5 Hz, 1 H, furyl), 6.28 (dd, J = 1.8, 3.5 Hz, 1 H, furyl).
13C{1H} NMR (100.6 MHz, CDCl3):  (E-isomer) = 197.7, 152.1, 144.5,
137.8, 137.3, 135.4, 135.0, 133.1, 130.1, 128.7, 128.6, 128.2, 126.9,
123.6, 121.5, 115.1, 112.3;  (Z-isomer) = 198.6, 151.0, 143.7, 137.4,
136.8, 136.4, 133.7, 132.1, 129.5, 128.8, 128.7, 128.4, 128.1, 126.6,
118.6, 111.9, 111.9.
HRMS (ESI-TOF): m/z calcd for [C23H17ClO + H]+: 345.1046; found:
345.1049.
(3E)-2-(4-(Dimethylamino)benzylidene)-1,4-diphenylbut-3-en-1-
one (3ad)
HRMS (ESI-TOF): m/z calcd for [C21H16O2 + H]+: 301.1229; found:
301.1194.
Following the general procedure, 3ad was prepared from (E)-1,4-di-
phenylbut-3-en-1-one (1a; 133 mg, 0.6 mmol) and 4-(dimethylami-
no)benzaldehyde (2d; 75 mg, 0.5 mmol); orange solid; yield: 34 mg
(19%); predominantly Z-isomer.
Funding Information
1H NMR (400.1 MHz, CDCl3):  (Z-isomer) = 8.09-8.07 (m, 2 H, C6H5),
7.53–7.50 (m, 1 H, C6H5), 7.42–7.39 (m, 2 H, C6H5), 7.34–7.32 (m, 2 H,
C6H5), 7.28–7.24 (m, 2 H, C6H5), 7.18–7.17 (m, 1 H, C6H5), 7.12 (d,
J = 8.6 Hz, 2 H, ArH), 7.04 (d, J = 16.4 Hz, 1 H, CH=CH), 6.78 (s, 1 H,
CH=), 6.48 (d, J = 8.6 Hz, 2 H, ArH), 6.22 (d, J = 16.4 Hz, 1 H, CH=CH),
2.87 (s, 6 H, CH3).
The reported study was funded by RFBR according to the research
project No. 18-33-00100.
R
u
si
a
n
F
o
u
n
d
ati
o
n
for
B
asi
c
R
esearc
h
(18-33-0
0
1
0
0)
Acknowledgment
13C{1H} NMR (100.6 MHz, CDCl3):  (Z-isomer) = 200.6, 150.0, 137.3,
136.3, 135.4, 133.8, 132.9, 130.4, 130.2, 129.7, 129.2, 128.9, 128.6,
127.4, 126.3, 123.2, 111.9, 40.1.
HRMS (ESI-TOF): m/z calcd for [C25H23NO + H]+: 354.1857; found:
354.1876.
The spectral data were obtained with the equipment of the Baikal An-
alytical Center for collective use SB RAS. We acknowledge Dr. A. V.
Kuzmin (Shared Research Facilities for Physical and Chemical Ultra-
microanalysis, Limnological Institute, SB RAS) for the recording of
HRMS spectra.
Supporting Information
Supporting information for this article is available online at
https://doi.org/10.1055/s-0039-1690003.
S
u
p
p
orti
n
gInformati
o
n
S
u
p
p
orti
n
gInformati
o
n
© 2019. Thieme. All rights reserved. — Synthesis 2019, 51, A–I

I
D. A. Shabalin et al.
Paper
Synthesis
References
(9) Sudhakar, G.; Raghavaiah, J.; Mahesh, G.; Singarapu, K. K. Org.
Biomol. Chem. 2016, 14, 2866.
(1) (a) Clarke, P. A.; Santos, S.; Martin, W. H. C. Green Chem. 2007, 9,
438. (b) Xiang, H.; Chen, Y.; He, Q.; Xie, Y.; Yang, C. RSC Adv.
2013, 3, 5807.
(2) (a) Trofimov, B. A.; Schmidt, E. Yu.; Ushakov, I. A.; Zorina, N. V.;
Skital’tseva, E. V.; Protsuk, N. I.; Mikhaleva, A. I. Chem. Eur. J.
2010, 16, 8516. (b) Trofimov, B. A.; Schmidt, E. Yu.; Zorina, N. V.;
Ivanova, E. V.; Ushakov, I. A. J. Org. Chem. 2012, 77, 6880.
(3) Trofimov, B. A.; Schmidt, E. Yu. Acc. Chem. Res. 2018, 51, 1117;
and reference cited therein.
(10) (a) Jones, G. Org. React. (N.Y.) 1967, 15, 204. (b) Tietze, L. F.;
Beifuss, U. The Knoevenagel Condensation, In Comprehensive
Organic Synthesis, Vol. 2; Trost, B. M.; Fleming, I.; Heathcock, C.
H., Ed.; Pergamon Press: Oxford, 1991, Chap. 1.11, 341–394.
(11) Schmidt, E. Yu.; Ivanova, E. V.; Tatarinova, I. V.; Ushakov, I. A.;
Semenova, N. V.; Vashchenko, A. V.; Trofimov, B. A. Org. Lett.
2016, 18, 2158.
(12) Zaid, Y.; Mboyi, C. D.; Drapeau, M. P.; Radal, L.; Chahdi, F. O.;
Rodi, Y. K.; Ollevier, T.; Taillefer, M. Org. Lett. 2019, 21, 1564.
(13) Vasil’ev, A. A.; Serebryakov, E. P. Russ. Chem. Rev. 2001, 70, 735.
(14) Mavrov, M. V.; Kucherov, V. F. Russ. Chem. Bull. 1962, 11, 1190.
(15) (a) Lantzsch, R.; Arlt, D. Liebigs Ann. Chem. 1976, 1757.
(b) Honek, J. F.; Mancini, M. L.; Belleau, B. Synth. Commun. 1984,
14, 483. (c) Hoffmann, H. M. R.; Eggert, U.; Poly, W. Angew.
Chem., Int. Ed. Engl. 1987, 26, 1015.
(4) Li, H.; Yin, L. Tetrahedron Lett. 2018, 59, 4121.
(5) (a) Zhu, B.; Zhang, W.; Lee, R.; Han, Zh.; Yang, W.; Tan, D.;
Huang, K.-W.; Jiang, Zh. Angew. Chem. Int. Ed. 2013, 52, 6666.
(b) Jing, Zh.; Bai, X.; Chen, W.; Zhang, G.; Zhu, B.; Jiang, Zh. Org.
Lett. 2016, 18, 260. (c) Han, M.-Y.; Luan, W.-Y.; Mai, P.-L.; Li, P.;
Wang, L. J. Org. Chem. 2018, 83, 1518.
(6) (a) Qiao, B.; Huang, Y.-J.; Nie, J.; Ma, J.-A. Org. Lett. 2015, 17,
4608. (b) Zhang, H.-J.; Shi, C.-Y.; Zhong, F.; Yin, L. J. Am. Chem.
Soc. 2017, 139, 2196.
(16) (a) Franck-Neumann, M.; Martina, D.; Brion, F. Angew. Chem.,
Int. Ed. Engl. 1981, 20, 864. (b) Colson, P. J.; Franck-Neumann,
M.; Sedrati, M. Tetrahedron Lett. 1989, 30, 2393.
(7) (a) Gu, Y.; Wang, Y.; Yu, T.-Y.; Liang, Y.-M.; Xu, P.-F. Angew.
Chem. Int. Ed. 2014, 53, 14128. (b) Zhan, G.; He, Q.; Yuan, X.;
Chen, Y.-C. Org. Lett. 2014, 16, 6000. (c) Iriarte, I.; Olaizola, O.;
Vera, S.; Gamboa, I.; Oiarbide, M.; Palomo, C. Angew. Chem. Int.
Ed. 2017, 56, 8860. (d) Akula, P. S.; Hong, B.-C.; Lee, G.-H. Org.
Lett. 2018, 20, 7835.
(17) Maercker, A.; van de Flierdt, J.; Girreser, U. Tetrahedron 2000,
56, 3373.
(18) Matsubara, S.; Ukai, K.; Toda, N.; Utimoto, K.; Oshima, K. Synlett
2000, 995.
(19) Nativi, C.; Taddei, M.; Mann, A. Tetrahedron 1989, 45, 1131.
(20) Choi, S. Y.; Chung, Y. K. Adv. Synth. Catal. 2011, 353, 2609.
(21) (a) The Chemistry of Dienes and Polyenes, Vol. 1; Rappoport, Z.,
Ed.; Wiley: Chichester, 1997. (b) The Chemistry of Dienes and
Polyenes, Vol. 2; Rappoport, Z., Ed.; Wiley: Chichester, 2000.
(8) Kong, X.; Song, J.; Liu, J.; Meng, M.; Yang, S.; Zeng, M.; Zhan, X.;
Li, C.; Fang, X. Chem. Commun. 2018, 54, 4266.
© 2019. Thieme. All rights reserved. — Synthesis 2019, 51, A–I