Cyclization of 1-Aryl-5-Phenylpent-4-en-2-yn-1-Ones to 2,3-Dihydropyran-2-Ones in Trifluoromethanesulfonic Acid

Article abstract of DOI:10.1007/s10593-020-02756-8

[Figure not available: see fulltext.] Under the action of an excess of trifluoromethanesulfonic acid, 1-aryl-5-phenylpent-4-en-2-yn-1-ones cyclize intramolecularly to 6-aryl-2-phenyl-2,3-dihydropyran-4-ones. The reaction proceeds at room temperature for 1

Full text of DOI:10.1007/s10593-020-02756-8

DOI 10.1007/s10593-020-02756-8
Chemistry of Heterocyclic Compounds 2020, 56(7), 953–956
Cyclization of 1-aryl-5-phenylpent-4-en-2-yn-1-ones
to 2,3-dihydropyran-2-ones in trifluoromethanesulfonic acid
Anna S. Zalivatskaya1,2, Aleksander А. Golovanov2,3, Aleksander V. Vasilyev1,2*
1 Saint Petersburg State Forest Technical University,
5 Institutskiy Pereulok, Saint Petersburg 194021, Russia; е-mail: aleksvasil@mail.ru
2 Institute of Chemistry, Saint Petersburg State University,
7/9 University Embankment, Saint Petersburg 199034, Russia
3 Togliatti State University,
14 Belorusskaya St., Togliatti 445020, Russia
Submitted June 3, 2020
Accepted July 17, 2020
Translated from Khimiya Geterotsiklicheskikh Soedinenii,
2020, 56(7), 953–956
Under the action of an excess of trifluoromethanesulfonic acid, 1-aryl-5-phenylpent-4-en-2-yn-1-ones cyclize intramolecularly to 6-aryl-
2-phenyl-2,3-dihydropyran-4-ones. The reaction proceeds at room temperature for 1 h with 50–60% yields.
Keywords: conjugated enynones, dihydropyranones, trifluoromethanesulfonic acid, carbocations, cyclization.
Various conjugated enynones are valuable compounds
for organic synthesis. Three important linearly or cross-
conjugated functional fragments are present in their
structure (multiple double and triple carbon–carbon bonds,
as well as a carbonyl group), that allow them to undergo a
variety of synthetic transformations. Nowadays, the
number of works devoted to the methods of synthesis of
organic compounds based on the enynone transformations
has increased.1 Nevertheless, linearly conjugated pent-4-en-
2-yn-1-ones 1 (Scheme 1) remain the least studied among
all possible conjugated enynones, probably due to the
complicated methods of their synthesis.
atom of the acetylene bond. Thus, intramolecular reactions
have been presented in which C-2 atom of the triple bond
acts as a nucleophilic center, which ultimately leads to
various carbocycles6 (Scheme 1).
Scheme 1. Literature data on synthetically
significant transformations of linearly conjugated
pent-4-en-2-yn-1-ones 1
It is known from the literature data that 1,5-diarylbut-
4-en-2-yn-1-ones interact at the C-3 atom of the acetylenic
bond to form dienone structures in reactions with
S-nucleophiles (Scheme 1).2 Enynones that do not contain
aryl substituents at the carbonyl group interact with
nucleophiles in
a similar way. For example, an
intramolecular cyclization with the participation of the
alkoxycarbonyl group and the C-3 atom of the triple bond
of enynes, catalyzed by gold complexes in the presence of
AcOH, has been described3,4 (Scheme 1). Nucleophilic
silylation of enynones and their carboxy analogs, catalyzed
by copper(II) complexes, occurs at the C-3 and C-5 atoms
of the enynone system, leading to the corresponding bisilyl
derivatives (Scheme 1).5 In contrast, the reactions of
enynones 1 with electrophilic reagents proceed at the C-2
Until now, the conversion of pent-4-en-2-yn-1-ones 1
under the action of various electrophilic reagents, such as
Brønsted or Lewis acids, has not been systematically
953
0009-3122/20/56(7)-0953©2020 Springer Science+Business Media, LLC

Chemistry of Heterocyclic Compounds 2020, 56(7), 953–956
studied. It can be assumed that protonation with Brønsted
enynones 1a–d in H2SO4 led to the formation of complex
mixtures possibly containing secondary products of
subsequent aromatic sulfonation.
Scheme 3. Cyclization of enynones 1a–d
into dihydropyranones 4a–d in TfOH
acids (or coordination with Lewis acids) of the basic
centers (multiple carbon–carbon bonds and oxygen atom of
the carbonyl group) of conjugated enynones 1 will lead to
the generation of highly reactive cationic species with
several electrophilic centers. This kind of species can
cyclize in superelectrophilic media, which opens up new
synthetic routes to practically significant functional
derivatives of heterocycles.1,7 Therefore, the aim of this
work is to study the transformations of 1,5-diarylpent-4-en-
2-yn-1-ones 1a–d in strong Brønsted acids H2SO4 and
TfOH (trifluoromethanesulfonic acid – superacid8).
A series of starting 1-aryl-5-phenylpent-4-en-2-yn-
1-ones 1a–d were synthesized in three steps (Scheme 2). In
the first step, dibromodiene 2 was formed in Wittig
reaction of cinnamaldehyde with CBr4 and PPh3. The
subsequent elimination of HBr by BuLi and hydrolysis
have led to 1-phenylbut-1-en-3-yn (3), which was cross-
coupled with aroyl chlorides under the Sonogashira
conditions to give the target enynones 1a–d in 40–61%
yields.
Additionally, we have studied the reaction of enynone
1b with less amount of TfOH (1.5 equiv). In this case, the
product of the Kucherov reaction – hydration of the
acetylene bond – enolic form of the corresponding
β-diketone 5а was isolated after chromatographic
separation on silica gel (Scheme 4). Apparently, compound
5а is formed as a result of the hydrolysis of the
intermediate vinyl triflate generated by the addition of
TfOH to the acetylene bond of the starting enynone 1b.
Scheme 2. Synthesis of conjugated enynones 1a–d
Scheme 4. Conversion of enynone 1b into compound 5a
under the action of 1.5 equiv of TfOH
The complex of the experimental data obtained in this
work, together with the results of our previous study on the
conversion of cross-conjugated enynones in acids7,
suggests possible mechanisms for the cyclization of
enynones 1a–d to dihydropyranones 4a–d (Scheme 5). The
initial protonation of the oxygen atom of the carbonyl
group of substrates 1 in TfOH leads to cations А↔А',
which, in turn, can be protonated at the acetylene bond in
the superacid TfOH with the formation of dications B. Both
species A and B can form O-protonated forms of vinyl
triflates C as a result of interaction with triflate anions TfO–.
In the case of small amounts of TfOH, the reaction stops at
this stage. Subsequent hydrolytic treatment of the reaction
mixtures leads to vinyl triflates D. The latter are,
apparently, unstable and hydrolyze rather rapidly to the
enol forms of diketones 5 upon storage in air or
chromatographic separation on silica gel (Scheme 4). In the
case when excess of TfOH is used, the reaction proceeds
further and cyclization of cations C to pyrans E occurs,
subsequent hydrolysis of which leads to the formation of
dihydropyranones 4. According to the literature data,7,9,10
cyclization of O-protonated enol forms C↔C' (or similar
enol structures) into pyrans E can proceed by two
alternative mechanisms: as coordinated 6π-electro-
cyclization (resonance form C) or nucleophilic addition
AdN (resonance form C') (Scheme 5). At this stage of the
study, it is difficult to postulate which mechanism is
We have found that under the action of an excess of
TfOH (15 equiv) enynones 1a–d cyclize to 6-aryl-2-phenyl-
2,3-dihydropyran-4-ones 4a–d at room temperature within
1 h in 50–60% yields (Scheme 3). The structures of
compounds 4a–d were established by 1H, 13C NMR
spectroscopy and high-resolution mass spectrometry. The
position of the double bond in the dihydropyranone system
of compounds 4b–d was additionally confirmed by the
NOESY experiment based on the correlations between the
vinyl proton of the pyranone ring and the ortho protons of
the neighboring aryl substituent. The following characte-
ristic signals of the dihydropyranone fragment are observed
1
in the H NMR spectra of dihydropyranones 4a–d: the
2-CH proton of the CHPh group at 5.56–5.59 ppm, the
5-CH vinyl proton at 6.09–6.13 ppm, as well as two
diastereotopic protons of the 3-СН2 group with a set of
signals characteristic for AB system at 2.73–2.75 and 2.96–
2.97 ppm. In the 13C NMR spectra, signals of carbon atoms
of the pyran structure C-2 and C-3 at 81.2 –81.4 and 43.0–
43.1 ppm, respectively, and carbonyl carbon atoms C=O at
192.8–193.3 ppm are present.
Earlier, structurally similar 2,3-dihydropyran-4-ones were
obtained by us as a result of cyclization of cross-conjugated
1,5-diarylpent-1-en-4-yn-3-ones (Ar–CH=CH–CO–C≡C–Ar')
in H2SO4.7 However, in the present work, the reactions of
954

Chemistry of Heterocyclic Compounds 2020, 56(7), 953–956
Scheme 5. Plausable mechanism for the conversion of enynones 1 under the action of TfOH
O
Ar
Ph
1
O
H+ (TfOH)
OH
H+
OH
Ar
Ph
O
4
Ar
Ph
Ar
C
B
Ph
Ph
A
OTf
O
TfO–
OTf OH
Ar
H2O
– TfOH
OTf
6 -electro-
cyclization
OH
TfO–, H+
Ph
Ar
Ar
Ar
Ar
– H+
C
Ph
Ph
H
C
A'
C
Ph
O
E
Ar
– H+
H2O
H2O
silica gel
OTf
OTf O
AdN
– H+
OH O
Ar
Ph
HC
Ph
D
5
O
H
C'
1
90.0°С (EtOH–H2O). Н NMR spectrum, δ, ppm (J, Hz):
followed in this cyclization. However, consideration that to
achieve the cyclization of cations C into pyrans E an
excess of the superacid TfOH is required, which promotes
the solvation of the intermediate cationic species, may
indicate the ionic nature of the key cyclization
intermediates, which possibly occurs in the case of the AdN
reaction.
3
6.38 (1H, d, J = 16.2, =СН); 7.34–7.40 (4H, m, H Ph,
=CH); 7.47–7.49 (2H, m, H Ph); 7.65 (2H, d, J = 8.6,
H Ar); 8.03 (2H, d, J = 8.6, H Ar). 13C NMR spectrum,
δ, ppm: 88.8; 93.7; 105.3; 127.2; 129.1; 129.6; 130.4;
131.1; 132.1; 135.2; 135.9; 148.4; 176.8. Found, m/z:
311.0073 [М+H]+. C17H12BrO. Calculated, m/z: 311.0066.
It is known that 2,3-dihydropyran-4-one fragment is
included into the structure of many natural and biologically
active compounds,11–13 therefore the development of the
methods for the preparation of 2,3-dihydropyran-4-one
derivatives is a promising trend of organic chemistry.
Thus, as a result of the study, a new method for the
synthesis of 2,3-dihydropyran-4-one derivatives by
cyclization of 1,5-diarylpent-4-en-2-yn-1-ones in trifluoro-
methanesulfonic acid has been developed.
Synthesis of 2,6-diaryl-2,3-dihydro-4H-pyran-4-ones
4a–d from enynones 1a–d in ТfOH (General method).
TfOH (0.11 ml, 1.29 mmol) was added with vigorous
stirring at room temperature to a solution of enynone 1a–d
(0.086 mmol) in CH2Cl2 (0.1 ml), the mixture was stirred
for 1 h. The reaction mixture was poured into H2O (50 ml),
extracted with CHCl3 (3×25 ml). The combined extracts
were washed with H2O (50 ml), aqueous NaHCO3 solution
(25 ml), again with H2O (25 ml) and dried with Na2SO4.
The solvent was removed under reduced pressure, the
product was isolated by preparative TLC on LS 5/40 μm
silica gel plates, eluent petroleum ether – EtOAc, 95:5. The
separated fractions were washed off from the sorbent with
CH2Cl2 .
Experimental
1H and 13C NMR spectra were recorded on a Bruker
AM-400 spectrometer (400 and 100 MHz, respectively) in
1
CDCl3. Residual solvent signals (7.26 ppm for H nuclei
and 77.0 ppm for 13C nuclei) were used as internal
standard. High-resolution mass spectra were recorded on a
Bruker micrOTOF instrument, electrospray ionization. The
reaction progress was monitored by TLC on Alugram SIL
G UV-254 plates. The reaction mixtures were separated by
column chromatography (on Merck 60 silica gel) or by
preparative TLC (on LS 5/40 silica gel plates), eluent
petroleum ether (fraction with bp 40–70°С) – EtOAc.
The synthesis and properties of the following
compounds were described previously: 1,1-dibromo-
4-phenylbuta-1,3-diene (2),14 1-phenylbut-1-en-3-yne (3),15
1,5-diphenylpent-4-en-2-yn-1-one (1a),16 1-(4-methylphenyl)-
5-phenylpent-4-en-2-yn-1-one (1b),16 1-(4-chlorophenyl)-
5-phenylpent-4-en-2-yn-1-one (1c).16
2,6-Diphenyl-2,3-dihydro-4H-pyran-4-one (4a).7 Yield
1
11 mg (50%). Pale-yellow solid. Mp 94–95°С. Н NMR
spectrum, δ, ppm (J, Hz): 2.75 (1H, AB system, ddd,
4
2J = 16.9, 3J = 3.4, J = 0.8, CH2); 2.97 (1H, AB system,
2
3
dd, J = 16.9, J = 14.1, CH2); 5.59 (1H, dd, 3J = 14.1,
3J = 3.4, CНPh); 6.13 (1H, d, 4J = 0.8, =CH); 7.41–7.47
(4H, m, H Ph); 7.48–7.52 (3H, m, H Ph); 7.77–7.80 (2H,
m, H Ph). 13C NMR spectrum, δ, ppm: 43.1 (3С); 81.2
(2С); 102.5; 126.3; 126.8; 128.9; 129.0 (2С); 131.9; 132.7;
138.5; 170.5; 193.1 (С=О). Found, m/z: 251.1073 [М+H]+.
C17H15O2. Calculated, m/z: 251.1067.
6-(4-Methylphenyl)-2-phenyl-2,3-dihydro-4H-pyran-
1
4-one (4b). Yield 10 mg (50%). Oil. Н NMR spectrum,
δ, ppm (J, Hz): 2.40 (1Н, s, CH3); 2.73 (1H, AB system,
2
3
4
(4E)-1-(4-Bromophenyl)-5-phenylpent-4-en-2-yn-1-one
(1d). Yield 200 mg (45%). Pale-yellow needles. Mp 89.5–
ddd, J = 16.9, J = 3.4, J = 0.9, CH2); 2.96 (1H, AB
system, dd, 2J = 16.9, 3J = 14.1, CH2); 5.56 (1H, dd, 3J = 14.1,
955

Chemistry of Heterocyclic Compounds 2020, 56(7), 953–956
3J = 3.4, CНPh); 6.12 (1H, d, 4J = 0.9, =CH); 7.25–7.27
m, H Ar); 7.68 (1H, d, 3J = 15.8, =CH); 7.94–7.97 (2H, m,
H Ar). 13C NMR spectrum, δ, ppm: 21.6; 97.6; 122.5;
127.5; 128.2; 128.8; 129.8; 132.5; 132.6; 136.5; 140.3;
140.6; 180.1; 189.1. Found, m/z: 265.1227 [М+H]+.
C18H17O2. Calculated, m/z: 265.1223.
(2H, m, H Ar); 7.39 (2H, d, J = 8.0, H Ar); 7.42–7.44 (2H,
m, H Ar); 7.47–7.51 (2H, m, H Ar); 7.76–7.79 (2Н, m,
H Ar). 13C NMR spectrum, δ, ppm: 21.4; 43.0 (3С); 81.2
(2С); 102.4; 126.4; 126.8; 128.8; 129.7; 131.9; 132.8;
135.4; 139.0; 170.6; 193.3 (С=О). Found, m/z: 265.1230
[М+H]+. C18H17O2. Calculated, m/z: 265.1223.
1
Supplementary information file containing Н and 13С
NMR spectra of all synthesized compounds, as well as
NOESY spectra of compounds 4c,d is available at the
journal website at http://link.springer.com/journal/10593.
6-(4-Chlorophenyl)-2-phenyl-2,3-dihydro-4H-pyran-
1
4-one (4c). Yield 13 mg (60%). Oil. Н NMR spectrum,
2
δ, ppm (J, Hz): 2.75 (1H, AB system, ddd, J = 16.9,
4
3J = 3.4, J = 0.9, CH2); 2.96 (1H, AB system, dd,
3
3
2J = 16.9, J = 14.1, CH2); 5.58 (1H, dd, 3J = 14.1, J = 3.4,
CНPh); 6.09 (1H, d, 4J = 0.9, =CH); 7.41 (2H, d, J = 8.8,
H Ar); 7.44–7.48 (5H, m, H Ph); 7.71 (2H, d, J = 8.8,
H Ar). 13C NMR spectrum, δ, ppm: 43.1 (3С); 81.4 (2С);
102.6; 126.4; 128.1; 129.0; 129.1; 129.2; 131.2; 138.1;
138.3; 169.2; 192.8 (С=О). Found, m/z: 285.0683 [М+H]+.
C17H14ClO2. Calculated, m/z: 285.0677.
This work was supported by the Russian Foundation for
Basic Research (grant 18-13-00008).
References
1. Golovanov, A. A.; Odin, I. S.; Zlotski, S. S. Russ. Chem. Rev.
2019, 88, 280. [Usp. Khim. 2019, 88, 280.]
2. Golovanov, A. A.; Gusev, D. M.; Zlotskii, S. S. Russ. J. Org.
Chem. 2016, 52, 1205. [Zh. Org. Khim. 2016, 52, 1212.]
3. Dhiman, S.; Ramasastry, S. S. V. Org. Lett. 2015, 17, 5116.
4. Mokar, B. D.; Liu, R.-S. Chem. Commun. 2014, 50, 8966.
5. Meng, F.-F.; Xie, J.-H.; Xu, Y.-H.; Loh, T.-P. ACS Catal.
2018, 8, 5306.
6-(4-Bromophenyl)-2-phenyl-2,3-dihydro-4H-pyran-
1
4-one (4d). Yield 10 mg (50%). Oil. Н NMR spectrum,
2
δ, ppm (J, Hz): 2.75 (1H, AB system, ddd, J = 17.0,
3J = 3.4, J = 0.9, CH2); 2.96 (1H, AB system, dd,
4
2J = 17.0, J = 14.1, CH2); 5.58 (1H, dd, J = 14.1,
3
3
3J = 3.4, CНPh); 6.10 (1H, d, J = 0.9, =CH); 7.42–7.50
4
6. Mondal, A.; Hazra, R.; Grover, K.; Raghu, M.; Ramasastry, S. S. V.
ACS Catal. 2018, 8, 2748.
7. Saulnier, S.; Lozovskiy, S. V.; Golovanov, A. A.; Ivanov, A. Yu.;
Vasilyev, A. V. Eur. J. Org. Chem. 2017, 3635.
8. Olah, G. A.; Prakash, G. K. S.; Sommer, J.; Molnar, A.
Superacid Chemistry; Wiley: New York, 2009, p. 525.
9. MacDonald, F. K.; Burnall, D. J. J. Org. Chem. 2009, 74, 6973.
10. Yang, F.; Ji, K.-G.; Zhao, S.-C.; Ali, S.; Ye, Y.-Y.; Liu, X.-Y.;
Liang, Y.-M. Chem.–Eur. J. 2012, 18, 6470.
11. Zheng, J.; Lin, L.; Fu, K.; Zhang, Y.; Liu, X.; Feng, X. Chem.–
Eur. J. 2014, 20, 14493.
12. Larrosa, I.; Romea, P.; Urpi, F. Tetrahedron 2008, 64, 2683.
13. Clarke, P. A.; Santos, S. Eur. J. Org. Chem. 2006, 2045.
14. Michaelides, I. N.; Darses, B.; Dixon, D. J. Org. Lett. 2011,
13, 664.
15. Torrado, A.; Lopez, S.; Alvarez, R.; de Lera, A. R. Synthesis
1995, 285.
16. Hoshi, M.; Yamazaki, H.; Okimoto, M. Synlett 2010, 2461.
(5H, m, H Ph); 7.57 (2H, d, J = 8.8, H Ar); 7.64 (2H, d,
J = 8.8, H Ar). 13C NMR spectrum, δ, ppm: 43.0 (3С); 81.4
(2С); 102.6; 126.4; 126.6; 128.3; 129.1 (2С); 132.2; 138.2;
169.4; 192.9 (С=О). Found, m/z: 329.0180 [М+H]+.
C17H14BrO2. Calculated, m/z: 329.0172.
(2Z,4E)-3-Hydroxy-1-(4-methylphenyl)-5-phenylpenta-
2,4-dien-1-one (5а) was synthesized according to the
general method for the preparation of compounds 4a–d
from enynone 1b (20 mg, 0.08 mmol) and TfOH (18 mg,
1.2 mmol) in CH2Cl2 (0.1 ml). The product was isolated by
column chromatography on silica gel, eluent petroleum
ether
– EtOAc, 99:1. Yield 14 mg (67%). Oil.
1Н NMR spectrum, δ, ppm (J, Hz): 2.39 (3Н, s, CH3); 6.34
3
(1H, s, =CH); 6.62 (1H, d, J = 15.8, =CH); 7.21 (2H, d,
J = 8.0, H Ar); 7.46–7.50 (4H, m, H Ar); 7.53–7.57 (1H,
956