Synthesis of polyfluorinated o-hydroxyacetophenones – convenient precursors of 3-benzylidene-2-phenylchroman-4-ones

Article abstract of DOI:10.1016/j.jfluchem.2019.109435

A simple and efficient approach to the synthesis of fluorinated o-hydroxyacetophenones in good to excellent yields is reported. We demonstrated a convenient method for replacing the iodine atom in o-iodophenols with MeC(O)-group through the introduction and subsequent hydrolysis of TIPS-CC-moiety by of p-toluenesulfonic acid monohydrate. The resulting compounds may serve as precursors for the synthesis of polyfluorinated 3-benzylidene-2-phenylchroman-4-one derivatives that are of interest as objects for the evaluation of their pharmacological properties.

Full text of DOI:10.1016/j.jfluchem.2019.109435

Journal Pre-proof
Synthesis of polyfluorinated o-hydroxyacetophenones – convenient
precursors of 3-benzylidene-2-phenylchroman-4-ones
Larisa Politanskaya, Evgeny Tretyakov, Chanjuan Xi
PII:
S0022-1139(19)30391-4
DOI:
https://doi.org/10.1016/j.jfluchem.2019.109435
FLUOR 109435
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Journal of Fluorine Chemistry
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2 November 2019
24 November 2019
24 November 2019
Please cite this article as: Politanskaya L, Tretyakov E, Xi C, Synthesis of polyfluorinated
o-hydroxyacetophenones – convenient precursors of 3-benzylidene-2-phenylchroman-4-ones,
Journal of Fluorine Chemistry (2019), doi: https://doi.org/10.1016/j.jfluchem.2019.109435
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Synthesis of polyfluorinated o-hydroxyacetophenones – convenient
precursors of 3-benzylidene-2-phenylchroman-4-ones
Larisa Politanskaya*1,2, Evgeny Tretyakov1,2, Chanjuan Xi3
a
N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch of Russian Academy
of Sciences, Ac. Lavrentiev Ave., 9, Novosibirsk 630090, Russian Federation
b Novosibirsk State University, Pirogova Street, 2, Novosibirsk 630090, Russian Federation
c
MOE Key Laboratory of Bioorganic Phosphorus Chemistry  Chemical Biology, Department of
Chemistry, Tsinghua University, Beijing 100084, China
Corresponding author. Tel.: +7-383-330-6859; fax: +7-383-330-9752; e-mail: plv@nioch.nsc.ru
Graphical Abstract
Highlights

A new convenient approach to the synthesis of o-hydroxyacetophenons from o-iodophenols
p-Toluenesulfonic acid – induced condensation of o-hydroxyacetophenons with
benzaldehyde into polyfluorinated 3-benzylidene-2-phenylchroman-4-one derivatives

Abstract
A simple and efficient approach to the synthesis of fluorinated o-hydroxyacetophenones in
good to excellent yields is reported. We demonstrated a convenient method for replacing
the iodine atom in o-iodophenols with MeC(=O)– group through the introduction and
subsequent hydrolysis of TIPS–CC– moiety by of p-toluenesulfonic acid monohydrate. The
resulting compounds may serve as precursors for the synthesis of polyfluorinated 3-
benzylidene-2-phenylchroman-4-one derivatives that are of interest as objects for the
evaluation of their pharmacological properties.
Key words fluorinated o-iodophenols, o-hydroxyacetophenones, palladium catalysis,
Sonogashira coupling, hydration reaction, aldol reaction
Introduction

o-Hydroxyacetophenones are useful organic compounds and versatile precursors in
synthesis of biologically active molecules such as chalcones [1], flavonols [2], flavanones
[3], benzopyrans [4], triazole-based acetophenones [5], thiazines [6], phenylpiperazines
[7], benzo[D]isoxazoles [8,9], chromane [4,10] and chromeno [11,12] derivatives. Although
the Fries rearrangement of acyloxybenzenes provides useful routes to acylphenols [1,2,4–
11,13–18], this thermally conducted reactions as a rule give rise to mixtures of o- and p-
substituted products [17]. Furthermore, the presence in the aromatic ring of phenols
electron acceptor substituents significantly complicates the course of this reaction,
proceeding by action of Lewis acids.
Thus, the development of regioselective approaches to the production of o-
hydroxyacetophenones from polyfluorinated phenols is an important synthetic task.
Because fluorine-containing compounds are of high interest in organic chemistry as they
have found in a wide range of applications, including in pharmaceuticals and medical
imaging [19,20]. Hereby, the aim of this work was to develop a selective approach to
polyfluorinated o-hydroxyacetophenones as promising precursors of fluorinated O-
heterocycles.
Results and Discussion
Previously, it has been found that fluorinated amino-substituted acetophenones can
be obtained by conversion of a Me3Si–CC– moiety into a MeC(=O)– group in the presence
of p-toluenesulfonic acid monohydrate (p-TSAH2O) [21]. In our opinion, this approach is
the most promising method to receive of fluorinated o-hydroxyacetophenones in view of
the acceptor nature of fluorine atoms in the substrates.
The starting materials for this study (a representative series of iodophenols
fluorinated to various degrees: 1a–f) were prepared according to our previously published
procedures [22]. It was found that fluorinated o-iodophenols interact with trimethylsilyl
(TMS)-acetylene thus yielding very volatile TMS-ethynylphenols or form a benzofuran
derivative (a byproduct) [22]. To avoid these side reactions and to decrease the volatility of
ethynyl derivatives, we decided to replace TMS substituent at the triple bond of the reagent
with a more voluminous and heavier triisopropylsilyl (TIPS) moiety.
The Sonogashira conditions and bis(triphenylphosphine) palladium dichloride,
copper(I) iodide, and triethylamine as catalysts in dry acetonitrile as a solvent caused the
cross-coupling of iodophenols 1a–f with TIPS-acetylene. The reactions were carried out at
room temperature in a tightly closed Schlenk flask in an argon atmosphere. As shown in
Table 1, in most cases, the reaction of iodophenols 1a–f with the TIPS-acetylene generated
TIPS-ethynylderivatives 2 in good to excellent yields. By the interaction of diiodophenols
1c,e with 0.9 or 2.2 equivalents of TIPS-acetylene under Sonogashira conditions,
compounds, we obtained compounds 2 containing one (2g,h) or two (2c,e) acetylene
groups, respectively (Table 1, entries 3, 5 and 7, 8). The target compounds were isolated by
thin-layer chromatography (TLC).
Table 1 Synthesis of fluorinated TIPS-ethynylphenols 2a–h

TIPS-
Entry Iodophenole 1
Arylacetylene 2
acetylene Yield (%)
(equiv)
1
1.1
1.1
2.2
1.1
2.2
1.1
0.9
0.9
95
98
85
96
87
70
65
72
2
3
4
5
6
7
8

It has been reported that the TMS group effectively activates the triple bond in
arylacetylene for the hydration reaction by action of p-TSAH2O (in contrast with the
hydrogen atom) [21]. Our experiments showed that a difluorinated TIPS derivative of
phenol (2a) has lower reactivity than structurally similar TMS derivative of aniline (4,5-
difluoro-2-(TMS-ethynyl)aniline [21]): 2a remained unchanged at reflux in EtOH in the
presence of p-TSAH2O for 24 h, whereas a derivative of aniline transformed into the
ketone under the same reaction conditions [21].
For this reason, we replaced EtOH (the solvent) with a higher-boiling aliphatic
alcohol: n-BuOH. Progress of the reaction was monitored by means of a decrease in the
relative integral intensity of 19F NMR signals belonging to the starting compound 2e in the
samples of the reaction mass. It was revealed that as much as 90 h is necessary to complete
the triple-bond hydration by p-TSAH2O in boiling n-BuOH (Scheme 1). During the isolation
of o-hydroxyacetophenone 3e by preparative TLC, there was a difficulty with reaction
product separation from the solvent, this problem significantly reduced the yield of the
target product (up to 30%).
Scheme 1 Preparation of o-hydroxyacetophenone 3e in system p-TSAH2O/n-BuOH
To solve this problem, we changed the experimental procedure, by going back to
ethanol as a solvent and by increasing the reaction temperature to 150 C. All the
experiments were conducted in a thick-walled flask with an air-tight screw cap. As
presented in Table 2, under these conditions, the triple bond was regioselectively hydrated,
thereby giving polyfluorinated o-hydroxy-substituted acetophenones 3 in high yields.
Table 2 Synthesis of fluorinated o-hydroxyacetophenone 3a–g
Entry Acetylene 2
Time, h
20
Arylketone 3
Yield (%)
83
1
2a

72
72
90
72
90
150
82
85
88
92
70
60
2
3
4
5
6
7
8
2b
2c
2d
2e
2f
2g
2h
72
67
It is noteworthy that compounds 2c and 2e, which contain two acetylene groups,
interacted with p-TSAH2O to generate the products corresponding to the hydration of only
one triple bond (Table 2, entries 3 and 5).
By action of p-TSAH2O at 150 C, iodinated substrate 2h (in contrast to compound
2g) not only underwent the reaction of triple-bond hydration but also lost an iodine atom
in product 3h (Table 2, entries 8 and 7). For an in-depth analysis of the transformations of
compounds 2h and 2g occurring under the studied reaction conditions, we studied the
composition of the reaction mixtures by 19F NMR spectroscopy, taking samples every
several hours during the reaction. The end of the experiments corresponded to the almost
complete disappearance of signals of fluorine atoms belonging to the initial compounds 2h
and 2g in the 19F NMR spectra. The dynamics of changes in the molar ratio of the reactions
products of are illustrated in Figures 1 and 2.

2h
3h
3i
100
80
60
40
20
0
2i
0
10
20
30
40
50
60
70
80
90
t (h)
Figure 1. Transformations of compounds 2h by action of p-TSAH2O in EtOH at 150 C
100
2g
3g
3a
80
60
40
20
0
0
20
40
60
80
100
120
140
160
180
200
t (h)
Figure 2. Transformations of compounds 2g by action of p-TSAH2O in EtOH at 150 C
Data analysis clarified the observed results. It turned out that the main direction of
the reaction of alkyne 2h with p-TSAH2O is first the loss of an iodine atom, resulting in 2i
and only then the addition of a water molecule, forming a ketone 3h. Consequently, the
process of aromatic electrophilic substitution of the iodine by the hydrogen atom prevails
over the reaction of triple bond hydration in 2h (Figure 1). On the contrary, alkyne 2g,
which does not contain a fluorine atom at the para-position toward the iodine atom (as in
alkyne 2h) practically does not lose iodine (2a is not detected in the reaction mixture) but
reacts with a molecule of water, thereby yielding ketone 3g. Ketone 3a forms only in small
amounts as a byproduct due to the slow decomposition of ketone 3g (Figure 2). Thus, the
prevalence of one of the two competing reactions proceeding by action of p-TSAH2O
(either substitution of an iodine atom or hydration of a triple bond) may depend on the
substituents in the aromatic substrate.

The proposed mechanism of methyl aryl ketone 3 formation from TIPS-substituted
arylacetylene 2 is shown in Scheme 2 and is consistent with our other study [21]. Initially,
the protonation of the alkynylphenol produces the vinyl carbocation stabilized by the o-
hydroxy group effect. Subsequent addition of an H2O molecule yields an enol tautomerizing
into the more stable keto form. At the next step, the alcohol’s O atom attacks the electrophilic
Si atom. The process is facilitated by the formation of an intramolecular hydrogen bond and
proceeds via the corresponding enol into aryl ketone 3.
Scheme 2 A proposed mechanism of compounds 3 formation
Previously, we have developed an one pot synthetic approach to diverse derivatives
of 2-aryl-2,3-dihydroquinolin-4(1H)-ones from 2-aminoacetophenone and benzaldehyde,
using p-TSAH2O as a catalyst and toluene a solvent [23]. In the present work, by means of
the same approach, we attempted the synthesis of polyfluorinated 2-arylchroman-4-ones:
oxygen-containing structural analogs of these aza-heterocyclic scaffolds. Fortunately, the
interaction of o-hydroxyacetophenone 3c, which contains a triple-bond moiety, with an
excess of 4-fluorobenzaldehyde in the presence of p-TSAH2O and drying agent (MgSO4) led
to the formation of product 4 in good yield (88%; Scheme 3). By analogy with the literature
data [23], we assume that the exocyclic double bonds have E-configuration in the structure
of compound 4.
the exocyclic double bonds have E-configuration
Scheme 3 Synthesis of fluorinated 3-benzylidene-8-cinnamoyl-2-phenylchroman-4-one 4
The structure of compound 4 indicates that during the reaction, water was attached
to the alkyne triple bond, with further interaction of the aldehyde carbonyl group with

three groups of methylene protons of the substrate. Additionally, intramolecular
cyclization took place giving rise to a chroman containing framework (Scheme 4).
Scheme 4 The hypothetical scheme of 4 formation
Therefore, it can be assumed that TIPS-ethynyl derivatives 2 can also be used as substrates
to produce fluorinated chroman derivatives. This hypothesis was proven experimentally
(Scheme 5).
Scheme
5
Synthesis of fluorinated 3-benzylidene-2-phenylchroman-4-one
5
and 2-
phenylchroman-4-one 6.
Conclusion
We carried out highly efficient and simple synthesis of polyfluorinated TIPS-
ethynylphenols from o-iodophenols and acetylene using readily available catalysts
(bis(triphenylphosphine) palladium dichloride, copper(I) iodide, triethylamine). Then we
developed p-TSAH2O–assisted synthesis of polyfluorinated o-hydroxy acetophenones 3 in
good to excellent yields by the hydration of TIPS-ethynylphenols in an ethanol medium.
This method is universal, simple, economical and metal-free. We established that o-
hydroxy acetophenones 3, as well as their precursor 2, can be used to obtain
polyfluorinated O-heterocycles (3-benzylidene-2-phenylchroman-4-one derivatives) owing
to their interaction with benzaldehyde in the presence of p-TSAH2O in a toluene medium.
Experimental section

General experimental procedures
All solvents were purified using standard procedures. Et3N, MeCN, toluene were
distilled and kept over CaH2 before to use. Fluorinated iodophenols were obtained
according to the method [22]. Other chemicals were obtained from commercial sources
and were used without further purification. Preparative thin-layer chromatography was
performed on Merck precoated silica gel 60 PF254 containing gypsum. Visualization of the
developed chromatograms was performed by UV light. NMR spectra were recorded on a
Bruker Avance-300 (300.13 MHz for 1H and 282.37 MHz for 19F), Avance-400 (400.13 MHz
1
1
for H, 376.44 MHz for 19F and 100.62 MHz for 13C) and DRX-500 (500.13 MHz for H,
125.76 MHz for 13C) spectrometers. Deuterochloroform (CDCl3) and acetone-d6 were used
as solvents, with residual CHCl3 (δH = 7.26 ppm) or CDCl3 (δC = 77.0 ppm) and acetone (δH =
2.15 ppm) or acetone-d6 (δC = 28.6 and 205.0 ppm) being employed as internal standards.
C6F6 (δF 163.0 ppm) was used as external references (19F NMR). 13C NMR spectra were
registered with C–H spin decoupling. Masses of molecular ions were determined by HRMS
on a DFS Thermo scientific instrument (EI, 70 eV) and on Agilent 7200 Accurate Mass Q-
TOF GC/MS (EI, 70 eV). Melting points were recorded on a Melter-Toledo FP81
Thermosystem apparatus. The IR spectra were recorded on a Bruker Vector 22
spectrometer (KBr or thin layer).
Interaction of iodophenols 1 with trialkylsilylacetylenes; General Procedure
To a solution of iodophenol 1 (1.5 mmol) and ethynyltriisopropylsilane (1.65 mmol
or 3.30 mmol for 2c,e) in MeCN (10 mL) in a Schlenk flask under argon, Pd(PPh3)2Cl2 (52
mg, 0.07 mmol), CuI (28 mg, 0.15 mmol) and Et3N (3 mL) were added. The mixture was
stirred at room temperature for 48 h. Then, the reaction suspension was placed directly
onto a chromatography plates (silica gel) and air-dried. The reaction products were
isolated by TLC using hexane as an eluent.
4,5-Difluoro-2-((triisopropylsilyl)ethynyl)phenol (2a)
Colorless oil; yield: 0.44 g (95%); Rf = 0.50 (hexane).
IR (neat): 3506, 2945, 1893, 2868, 2146, 1633, 1606, 1504, 1464, 1346, 1319, 1248, 1219,
1
1188, 1149, 997, 881, 860, 756, 727, 677, 609, 499, 459 cm–1. H NMR (300 MHz, Acetone-
d6): δ = 7.13 (dd, J (H3,F4) = 10.2 Hz, J (H3,F5) = 8.6 Hz, 1 H, H3), 6.74 (dd, J (H6,F5) = 11.3 Hz,
J (H6,F4) = 6.9 Hz, 1 H, H6), 1.12 (s, 18 H, H10), 1.11 (s, 3 H, H9). 13C NMR (126 MHz, CDCl3): δ
3
1
2
= 154.1 (dm, J (C1,F5) = 10.5 Hz, C1), 151.3 (dd, J (C5,F5) = 251.9 Hz, J (C5,F4) = 14.1 Hz,
C5), 144.1 (dd, J (C4,F4) = 241.4 Hz, J (C4,F5) = 13.5 Hz, C4), 118.9 (dd, J (C3,F4) = 19.7 Hz,
C3), 105.4 (m, 3J (C2,F4) = 7.5 Hz, C2), 104.0 (d, 2J (C6,F5) = 21.2 Hz, C6), 99.4 (m, C7), 99.0 (m,
C8), 18.4 (s, C10), 11.1 (s, C9). 19F NMR (282 MHz, Acetone-d6): δ = –132.9 (m, J (F5,F4) = 22.0
Hz, J (F5,H6) = 11.3 Hz, J (F5,H3) = 8.6 Hz,1 F, F5), –149.2 (m, J (F4,F5) = 22.0 Hz, J (F4,H3) =
10.2 Hz, J (F4,H6) = 6.9 Hz,1 F, F4). HRMS (EI): m/z [M]+ calcd for C17H24F2SiO: 310.1559;
found: 310.1555.
1
2
2
2,4-Difluoro-6-((triisopropylsilyl)ethynyl)phenol (2b)

Yellowish oil; yield: 0.45 g (98%); Rf = 0.50 (hexane). IR (neat): 3508, 3089, 2945, 2893,
2866, 2152, 1601, 1485, 1466, 1444, 1367, 1350, 1338, 1255, 1219, 1186, 1122, 1072,
1
1012, 993, 920, 883, 858, 796, 692, 677, 596, 569, 530, 501 cm–1. H NMR (300 MHz,
Acetone-d6): δ = 8.81 (s, 1 H, OH), 7.05 (m, J (H5,F6) = 10.7 Hz, J (H5,F4) = 8.6 Hz, J (H5,H3) =
3.1 Hz, 1 H, H5), 6.97 (dm, J (H3,F4) = 8.7 Hz, J (H3,H5) = 3.1 Hz, 1 H, H3), 1.14 (s, 21 H, 18 H10
+ 3 H9). 13C NMR (126 MHz, CDCl3): δ = 155.3 (dd, 1J (C4,F4) = 239.1 Hz, 3J (C4,F6) = 11.9 Hz,
1
3
2
C4), 152.1 (dd, J (C6,F6) = 242.2 Hz, J (C6,F4) = 13.1 Hz, C6), 144.2 (dd, J (C1,F6) = 15.0 Hz,
2
3
2
C1), 115.0 (dd, J (C3,F4) = 23.8 Hz, C3), 114.4 (dd, J (C2,F4) = 11.1 Hz, C2), 105.8 (dd, J
(C5,F6) = 27.3 Hz, 2J (C5,F4) = 23.1 Hz, C5), 101.8 (m, C7), 97.8 (s, C8), 19.0 (s, C10), 12.0 (s, C9).
19F NMR (282 MHz, Acetone-d6): δ = –121.6 (td, J (F4,H3) ≈ J (F4,H5) = 8.6 Hz, J (F4,F6) = 1.9
Hz,1 F, F4), –131.1 (dm, J (F6,H5) = 10.7 Hz, J (F6,F4) = 1.9 Hz, 1 F, F6). HRMS (EI): m/z [M]+
calcd for C17H24F2SiO: 310.1559; found: 310.1556.
3,4-Difluoro-2,6-bis((triisopropylsilyl)ethynyl)phenol (2c)
Colorless oil; yield: 0.62 g (85%); Rf = 0.75 (hexane). IR (neat): 3502, 2945, 2893, 2868,
2154, 2063, 1616, 1496, 1483, 1458, 1431, 1385, 1367, 1317, 1280, 1238, 1194, 1072,
1
1018, 995, 928, 883, 729, 677, 663, 627, 459 cm–1. H NMR (300 MHz, Acetone-d6): δ =
7.35(dd, J (H5,F4) = 10.5 Hz, J (H5,F3) = 8.8 Hz, 1 H, H5), 1.15 – 1.13 (m, 42 H, 18 H10 + 18 H10’
1
+ 3 H9 + 3 H9’). 13C NMR (126 MHz, Acetone-d6): δ = 157.5 (s, C1), 152.8 (dd, J (C3,F3) =
2
1
2
254.0 Hz, J (C3,F4) = 14.4 Hz, C3), 145.0 (dd, J (C4,F4) = 240.0 Hz, J (C4,F3) = 13.0 Hz, C4),
121.8 (dd, 2J (C5,F4) = 19.7 Hz, C5), 108.4 (m, 3J (C6,F4) = 8.1 Hz, C6), 105.1 (m, C7’), 104.2 (dd,
2J (C2,F3) = 15.5 Hz, C2), 101.4 (m, C7), 98.4 (m, C8’), 19.5 (s, C10), 19.5 (s, C10’), 12.5 (s, C9),
12.5 (s, C9’). 19F NMR (282 MHz, Acetone-d6): δ = –129.7 (dd, J (F3,F4) = 22.0 Hz, J (F3,H5) =
8.8 Hz, 1 F, F3), –147.2 (dd, J (F4,F3) = 22.0 Hz, J (F4,H5) = 10.5 Hz, 1 F, F4). HRMS (EI): m/z
[M]+ calcd for C28H44F2Si2O: 490.2893; found: 490.2886.
2,3,4-Trifluoro-6-((triisopropylsilyl)ethynyl)phenol (2d)
Colorless oil; yield: 0.47 g (96%); Rf = 0.60 (hexane). IR (neat): 3585, 3500, 2945, 2893,
2868, 2146, 1610, 1523, 1483, 1385, 1373, 1321, 1236, 1198, 1043, 997, 935, 883, 856,
1
729, 679, 567, 521, 470, 440 cm–1. H NMR (300 MHz, CDCl3): δ = 6.97 (m, J (H5,F4) = 10.1
Hz, J (H5,F3) = 7.8 Hz, J (H5,F2) = 2.4 Hz, 1 H, H5), 1.13 – 1.10 (m, 21 H, 18 H10 + 3 H9). 13C
1
2
NMR (126 MHz, CDCl3): δ = 144.4 (dm, J (C4,F4) = 243.1 Hz, J (C4,F3) = 10.8 Hz, C4), 143.3
(dm, 2J (C1,F2) = 9.9 Hz, C1), 141.4 (dm, 1J (C3,F3) = 253.6 Hz, 2J (C3,F2) = 16.4 Hz, 2J (C3,F4) =
12.2 Hz, C3), 140.3 (dm, J (C2,F2) = 248.8 Hz, J (C2,F3) = 12.1 Hz, C2), 113.1 (dd, J (C5,F4) =
19.9 Hz, C5), 105.8 (m, C6), 100.9 (m, C7), 97.8 (m, C8), 18.5 (s, C10), 11.0 (s, C9). 19F NMR
(282 MHz, CDCl3): δ = –143.5 (dd, J (F4,F3) = 21.2 Hz, J (F4,H5) = 10.1 Hz, 1 F, F4), –153.4 (m,
J (F3,F4) = 21 Hz, J (F3,F2) = 19.6 Hz, J (F3,H5) = 7.8 Hz, 1 F, F3), –154.0 (dm, J (F2,F3) = 19.6
Hz, J (F2,H5) = 2 Hz, 1 F, F2). HRMS (EI): m/z [M]+ calcd for C17H23F3SiO: 328.1465; found:
328.1463.
1
2
2
3,4,5-Trifluoro-2,6-bis((triisopropylsilyl)ethynyl)phenol (2e)
Colorless oil; yield: 0.66 g (87%); Rf = 0.42 (hexane). IR (neat): 3500, 2945, 2893, 2868,
2156, 1614, 1496, 1473, 1406, 1385, 1317, 1236, 1130, 1072, 985, 960, 920, 883, 775, 714,
1
677, 663, 629, 565, 449 cm–1. H NMR (300 MHz, Acetone-d6): δ = 1.14 – 1.13 (m, 18 H10
+

3
18 H10’ + 3 H9 + 3 H9’). 13C NMR (126 MHz, Acetone-d6): δ = 156.7 (tm, J (C1,F3) = 4.8 Hz,
C1), 153.1 (dm, 1J (C3,F3) = 253.1 Hz, 2J (C3,F4) = 11.2 Hz, C3), 135.2 (dt, 1J (C4,F4) = 242.4 Hz,
2
2J (C4,F3) = 15.8 Hz, C4), 104.0 (m, C5), 99.5 (dm, J (C2,F3) = 13.8 Hz, C2), 93.8 (m, C6), 18.9
(s, C8), 11.9 (s, C7). 19F NMR (282 MHz, Acetone-d6): δ = –129.0 (d, J (F3,F4) = 22.0 Hz, 2 F,
F3), –170.2 (t, J (F4,F3) = 22.0 Hz, 1 F, F4). HRMS (EI): m/z [M]+ calcd for C28H43F3Si2O:
508.2800; found: 508.2799.
2,3,4,5-Tetrafluoro-6-((triisopropylsilyl)ethynyl)phenol (2f)
Colorless oil; yield: 0.36 g (70%); Rf = 0.85 (hexane). IR (neat): 3583, 3498, 2947, 2893,
2868, 2158, 1657, 1620, 1522, 1502, 1466, 1385, 1327, 1232, 1136, 1072, 995, 966, 883,
1
683, 644, 592, 563, 515 cm–1. H NMR (300 MHz, Acetone-d6): δ = 1.14 – 1.13 (m, 18 H10
+
18 H10’ + 3 H9 + 3 H9’). 13C NMR (126 MHz, Acetone-d6): δ = 149.0 (dm, 1J (C3,F3) = 246.0 Hz,
C3), 145.5 (dm, J (C1,F6) = 13.2 Hz, C1), 142.6 (dm, J (C5,F5) = 250.7 Hz, C5), 139.0 (m, J
2
1
1
(C6,F6) = 240.1 Hz, C6), 134.6 (dm, J (C4,F4) = 241.5 Hz, C4), 103.4 (m, C7), 99.8 (dm, J
(C2,F3) = 16.5 Hz, C2), 94.1 (m, C8), 18.9 (s, C10), 11.9 (s, C9). 19F NMR (282 MHz, Acetone-d6):
δ = –138.4 (ddd, J (F3,F4) = 22.3 Hz, J (F3,F6) = 8.6 Hz, 1 F, F3), –156.6 (tm, J (F5,F6) ≈ J (F5,F4)
= 20.6 Hz, 1 F, F5); –162.4 (ddd, J (F6,F5) = 20.5 Hz, J (F6,F3) = 8.6 Hz, 1 F, F6); –171.4 (t, J
(F4,F5) ≈ J (F4,F3) ≈ 20 Hz, 1 F, F4). HRMS (EI): m/z [M]+ calcd for C17H22F4SiO: 346.1371;
found: 346.1369.
1
2
3,4-Difluoro-2-iodo-6-((triisopropylsilyl)ethynyl)phenol (2g)
Colorless oil; yield: 0.42 g (65%); Rf = 0.22 (hexane). IR (neat): 3491, 2945, 2891, 2866,
2146, 1583, 1504, 1471, 1421, 1385, 1352, 1311, 1234, 1199, 1072, 995, 908, 881, 864,
1
827, 729, 677, 631, 548, 499, 467 cm–1. H NMR (300 MHz, Acetone-d6): δ = 7.37(dd, J
(H5,F4) = 10.3 Hz, J (H5,F3) = 8.8 Hz, 1 H, H5), 1.12 – 1.11 (m, 21 H, 18 H10 + 3 H9). 13C NMR
1
2
(126 MHz, Acetone-d6): δ = 155.7 (m, C1), 151.9 (dd, J (C3,F3) = 242.1 Hz, J (C3,F4) = 14.8
Hz, C3), 144.0 (dd, J (C4,F4) = 243.4 Hz, J (C4,F3) = 14.7 Hz, C4), 120.8 (dd, J (C5,F4) = 19.7
Hz, C5), 107.0 (m, 3J (C6,F4) = 7.5 Hz, C6), 100.6 (m, C7), 98.5 (m, C8), 75.2 (d, 2J (C2,F3) = 24.3
Hz, C2), 18.9 (s, C9), 11.9 (s, C9). 19F NMR (282 MHz, Acetone-d6): δ = –110.4 (dd, J (F3,F4) =
24.2 Hz, J (F3,H5) = 8.8 Hz, 1 F, F3), –144.7 (dd, J (F4,F3) = 24.2 Hz, J (F4,H5) = 10.3 Hz, 1 F, F4).
HRMS (EI): m/z [M]+ calcd for C17H23F2ISiO: 436.0525; found: 436.0531.
1
2
2
3,4,5-Trifluoro-2-iodo-6-((triisopropylsilyl)ethynyl)phenol (2h)
Colorless oil; yield: 0.49 g (72%); Rf = 0.34 (hexane, twice). IR (neat): 3489, 2945, 2893,
2868, 2154, 1630, 1593, 1491, 1462, 1388, 1313, 1217, 1072, 1018, 997, 966, 920, 883,
804, 742, 679, 663, 634, 499, 472, 445 cm–1. 1H NMR (300 MHz, Acetone-d6): δ = 1.12 – 1.11
(m, 18 H10 + 3 H9). 13C NMR (126 MHz, Acetone-d6): δ = 155.5 (m, C1), 153.1 (dm, 1J (C5,F5) =
2
1
2
249.8 Hz, J (C5,F4) = 10.4 Hz, C5), 152.4 (dm, J (C3,F3) = 244.1 Hz, J (C3,F4) = 11.4 Hz, C3),
134.5 (dm, 1J (C4,F4) = 244.7 Hz, 2J (C4,F5) ≈ 2J (C4,F3) = 18.7 Hz, C4), 104.3 (m, C7), 98.7 (dm,
2J (C2,F3) = 16.0 Hz, C2), 94.2 (m, C8), 69.4 (dm, 2J (C6,F5) = 24.5 Hz, C6), 18.9 (s, C10), 11.9 (s,
C9). 19F NMR (282 MHz, Acetone-d6): δ = –109.9 (dd, J (F5,F4) = 24.0 Hz, J (F5,F3) = 7.2 Hz, 1
F, F5), –130.8 (dd, J (F3,F4) = 21.1 Hz, J (F3,F5) = 7.2 Hz, 1 F, F3), –168.4 (dd, J (F4,F5) = 24.0
Hz, J (F4,F3) = 21.1 Hz, 1 F, F4). HRMS (EI): m/z [M]+ calcd for C17H22F3ISiO: 454.0431;
found: 454.0436.

3,4,5-Trifluoro-2-((triisopropylsilyl)ethynyl)phenol (2i)
Colorless oil; yield: 0.12 g (25%); Rf = 0.42 (hexane, twice). IR (neat): 3504, 2945, 2893,
2868, 2154, 1649, 1610, 1512, 1469, 1396, 1369, 1315, 1238, 1198, 1155, 1059, 997, 939,
1
883, 837, 750, 677, 609, 472, 442 cm–1. H NMR (300 MHz, Acetone-d6): δ = 6.71(m, J
(H6,F5) = 12.0 Hz, J (H6,F4) = 6.4 Hz, J (H6,F3) = 2.3 Hz,1 H, H6), 1.14 (m, 21 H, 18 H10 + 3 H9).
1
2
13C NMR (126 MHz, Acetone-d6): δ = 154.4 (m, C1), 151.6 (dm, J (C3,F3) = 249.8 Hz, J
(C3,F4) = 10.8 Hz, C3), 150.2 (dm, J (C5,F5) = 249.3 Hz, J (C5,F4) = 10.7 Hz, C5), 133.0 (dt, J
1
2
1
(C4,F4) = 241.1 Hz, J (C4,F5) ≈ J (C4,F3) = 15.9 Hz, C4), 100.6 (m, C7), 98.7 (dm, J (C6,F5) =
2
2
2
20.7 Hz, C6), 97.5 (dm, J (C2,F3) = 15.6 Hz, C2), 93.4 (m, C8), 17.5 (s, C10), 10.4 (s, C9). 19F
2
NMR (282 MHz, Acetone-d6): δ = –131.3 (dm, J (F3,F4) = 21.4 Hz, J (F3,F5) = 6.4 Hz, J (F3,H6) =
2.3 Hz,1 F, F3), –132.6 (m, J (F5,F4) = 21.8 Hz, J (F5,H6) = 12.0 Hz, J (F5,F3) = 6.4 Hz,1 F, F5), –
172.7 (m, J (F4,F5) ≈ J (F4,F3) = 21.6 Hz, J (F4,H6) = 6.4 Hz, 1 F, F4). HRMS (EI): m/z [M]+ calcd
for C17H23F3SiO: 328.1465; found: 328.1470.
Interaction of triisopropilsilylacetylenes 2 with p-toluenesulfonic acid monohydrate in
EtOH; General Procedure
To a solution of acetylene 2 (1.0 mmol) in EtOH (4 mL) in an ace pressure tube under argon
p-TSA monohydrate (380 mg, 2.0 mmol) was added, and the flask was hermetically closed
with a screw cap. The mixture was heated at 150 C (the temperature in the thermostat)
with stirring (reaction time see in Table 2). The mixture was allowed to cool to room
temperature, placed directly onto a chromatography plates (silica gel) and air-dried. The
methyl aryl ketone 3 was isolated by TLC using hexane as an eluent.
1-(4,5-Difluoro-2-hydroxyphenyl)ethanone (3a)
White solid; yield: 0.14 g (83%); Rf = 0.33 (hexane, twice); mp 40.9 – 43.5 °C. IR (KBr):
3070, 2931, 1653, 1630, 1606, 1514, 1427, 1373, 1325, 1298, 1248, 1188, 1153, 1047, 956,
1
885, 831, 781, 740, 677, 650, 551 cm–1. H NMR (300 MHz, Acetone-d6): δ = 12.40 (s, 1H,
OH), 7.93 (dd, J (H3,F4) = 11.1 Hz, J (H3,F5) = 9.0 Hz, 1 H, H3), 6.88 (dd, J (H6,F5) = 12.0 Hz, J
(H6,F4) = 6.9 Hz, 1 H, H6), 2.67 (s, 3 H, CH3). 13C NMR (126 MHz, Acetone-d6): δ = 204.7 (m,
3
1
2
C7), 161.0 (dm, J (C1,F5) = 11.8 Hz, C1), 155.9 (dd, J (C5,F5) = 256.2 Hz, J (C5,F4) = 14.2 Hz,
1
2
2
C5), 143.9 (dd, J (C4,F4) = 239.1 Hz, J (C4,F5) = 13.5 Hz, C4), 119.8 (dd, J (C3,F4) = 18.8 Hz,
C3), 116.7 (m, C2), 107.1 (d, J (C6,F5) = 19.8 Hz, C6), 27.1 (s, C8). 19F NMR (282 MHz,
2
Acetone-d6): δ = –124.8 (m, J (F5,F4) = 22 Hz, J (F5,H6) = 12.0 Hz, J (F5,H3) = 9.0 Hz,1 F, F5), –
148.5 (m, J (F4,F5) = 22.0 Hz, J (F4,H3) = 11.1 Hz, J (F4,H6) = 6.9 Hz,1 F, F4). HRMS (EI): m/z
[M]+ calcd for C8H6F2O2: 172.0330; found: 172.0335.
1-(3,5-Difluoro-2-hydroxyphenyl)ethanone (3b)
White solid; yield: 0.14 g (82%); Rf = 0.39 (hexane, 5 times); mp 106.5 – 108.3 °C. IR (KBr):
3080, 2943, 2866, 1655, 1628, 1606, 1452, 1369, 1313, 1269, 1217, 1155, 1115, 1012, 972,
1
885, 875, 800, 663, 600, 459, 434 cm–1. H NMR (300 MHz, Acetone-d6): δ = 12.01 (s, 1 H,
OH), 7.56 (dm, J (H3,F4) = 9.0 Hz, J (H3,H5) = 3.0 Hz, J (H3,F6) = 1.9 Hz, 1 H, H3), 7.384 (m, J
(H5,F6) = 10.8 Hz, J (H5,F4) = 8.5 Hz, J (H5,H3) = 3.0 Hz, 1 H, H5), 2.69 (s, 3 H, CH3). 13C NMR

1
3
(126 MHz, Acetone-d6): δ = 205.5 (m, C7), 154.3 (dd, J (C4,F4) = 238.8 Hz, J (C4,F6) = 10.5
Hz, C4), 152.0 (dd, J (C6,F6) = 249.0 Hz, J (C6,F4) = 11.7 Hz, C6), 148.2 (dd, J (C1,F6) = 12.5
1
3
2
3
2
2
Hz, C1), 121.6 (dd, J (C2,F4) = 7.7 Hz, C2), 112.5 (dd, J (C3,F4) = 23.3 Hz, C3), 111.6 (dd, J
(C5,F6) = 27.7 Hz, 2J (C5,F4) = 21.5 Hz, C5), 27.4 (s, C8). 19F NMR (282 MHz, Acetone-d6): δ = –
121.6 (td, J (F4,H3) ≈ J (F4,H5) = 8.7 Hz, J (F4,F6) = 1.5 Hz,1 F, F4), –132.2 (dt, J (F6,H5) = 10.8
Hz, J (F6,F4) ≈ J (F6,H3) = 1.7 Hz, 1 F, F6). HRMS (EI): m/z [M]+ calcd for C8H6F2O2: 172.0330;
found: 172.0332.
1-(2,3-Difluoro-6-hydroxy-5-((triisopropylsilyl)ethynyl)phenyl)ethanone (3c)
White solid; yield: 0.30 g (85%); Rf = 0.31 (hexane, twice); mp 57.3 – 60.9 °C. IR (KBr):
2943, 2893, 2866, 2162, 1649, 1595, 1495, 1466, 1429, 1369, 1327, 1282, 1209, 1192,
1078, 1018, 997, 960, 883, 868, 831, 696, 673, 660, 596, 553, 465 cm–1. 1H NMR (300 MHz,
Acetone-d6): δ = 12.97 (s, 1 H, OH), 7.95(dd, J (H5,F4) = 10.9 Hz, J (H5,F3) = 8.9 Hz, 1 H, H5),
2.68 (s, 3 H, CH3), 1.14 – 1.13 (m, 21 H, 18 H12 + 3 H11). 13C NMR (126 MHz, Acetone-d6): δ =
1
2
204.8 (m, C7), 162.3 (m, C1), 156.4 (dd, J (C3,F3) = 259.9 Hz, J (C3,F4) = 14.7 Hz, C3), 143.6
(dd, J (C4,F4) = 239.7 Hz, J (C4,F3) = 13.0 Hz, C4), 119.7 (dd, J (C5,F4) = 19.0 Hz, C5), 116.2
(m, 3J (C6,F4) = 5.3 Hz, C6), 104.5 (d, 2J (C2,F3) = 14.2 Hz, C2), 104.3 (m, C9), 94.3 (m, C10), 27.1
(s, C8), 18.9 (s, C12), 11.9 (s, C11). 19F NMR (282 MHz, Acetone-d6): δ = –121.4 (dd, J (F3,F4) =
22.3 Hz, J (F3,H5) = 8.9 Hz, 1 F, F3), –147.6 (br. m, 1 F, F4). HRMS (EI): m/z [M]+ calcd for
C19H26F2SiO2: 352.1665; found: 352.1661.
1
2
2
1-(3,4,5-Trifluoro-2-hydroxyphenyl)ethanone (3d)
White solid; yield: 0.17 g (88%); Rf = 0.50 (hexane, twice); mp 56.9 °C (decomp.). IR (KBr):
2933, 2864, 1718, 1664, 1523, 1462, 1381, 1309, 1271, 1199, 1080, 1030, 962, 866, 781,
1
690, 604, 519 cm–1. H NMR (500 MHz, Acetone-d6): δ = 7.79 (br. t, J (H3,F4) ≈ J (H3,F5) = 9
Hz, 1 H, H3), 2.68 (s, 3 H, CH3). 13C NMR (126 MHz, Acetone-d6): δ = 204.8 (br. s, C7), 150.4
(br. s, C1), 145.2 (dm, 1J (C5,F5) = 246.2 Hz, 2J (C5,F4) = 16.4 Hz, 2J (C5,F6) = 12.6 Hz, C5), 143.5
1
1
(br. d, J (C6,F6) ≈ 250 Hz, C6), 143.5 (br. d, J (C4,F4) ≈ 250 Hz, C4), 116.6 (br. s, C2), 113.6
(dm, 2J (C3,F4) = 19.3 Hz, C3), 27.4 (s, C8). 19F NMR (282 MHz, Acetone-d6): δ = –147.2 (br. s,
1 F, F4), –149.0 (br. s, 1 F, F5), –157.3 (br. d, J (F6,F5) ≈ 17 Hz, 1 F, F6). 19F NMR (282 MHz,
CDCl3): δ = –146.7 (dd, J (F4,F5) = 21.6 Hz, J (F4,H3) = 10.2 Hz, 1 F, F4), –147.5 (m, J (F5,F4) =
21.6 Hz, J (F5,F6) = 18.6 Hz, J (F5,H3) = 7.9 Hz, 1 F, F5), –156.7 (dd, J (F6,F5) = 18.6 Hz, J
(F6,H3) = 2.4 Hz, 1 F, F6). HRMS (EI): m/z [M]+ calcd for C8H9F3O: 190.0236; found:
190.0234.
1-(2,3,4-Trifluoro-6-hydroxy-5-((triisopropylsilyl)ethynyl)phenyl)ethanone (3e)
White solid; yield: 0.34 g (92%); Rf = 0.67 (hexane, twice); mp 39.2 – 40.5 °C. IR (KBr):
3500, 2943, 2893, 2868, 2727, 2156, 1614, 1496, 1471, 1385, 1317, 1236, 1122, 1103,
1
1070, 985, 960, 920, 883, 773, 719, 679, 659, 453 cm–1. H NMR (300 MHz, CDCl3): δ =
13.25 (s, 1 H, OH), 2.66 (d, 3 H, CH3), 1.12 – 1.11 (m, 21 H, 18 H12 + 3 H11). 13C NMR (126
MHz, CDCl3): δ = 201.2 (t, C7), 161.0 (t, C1), 156.5 (dm, 1J (C3,F3) = 261.8 Hz, 2J (C3,F4) = 11.1
Hz, C3), 151.7 (dm, 1J (C5,F5) = 260.3 Hz, 2J (C5,F4) = 11.3 Hz, C5), 133.4 (dt, 1J (C4,F4) = 244.6
2
2
2
2
Hz, J (C4,F5) ≈ J (C4,F3) = 15.8 Hz, C4), 106.5 (dm, J (C2,F3) = 11.8 Hz, C2), 100.2 (dd, J
(C6,F5) = 15.2 Hz, C6), 31.9 (d, J (C8,F) = 10.7 Hz, C8), 18.4 (s, C12), 11.1 (s, C11). 19F NMR (282

MHz, CDCl3): δ = –119.6 (dd, J (F3,F4) = 22.7 Hz, J (F3,F5) = 14.6 Hz, 1 F, F3), –128.6 (m, J
(F5,F4) = 22 Hz, J (F5,F3) = 14.6 Hz, 1 F, F5), –172.3 (br. t, 1 F, F4). HRMS (EI): m/z [M]+ calcd
for C19H25F3SiO2: 370.1570; found: 370.1574.
1-(2,3,4,5-Tetrafluoro-6-hydroxyphenyl)ethanone (3f)
Colorless oil; yield: 0.14 g (70%); Rf = 0.59 (hexane, twice). IR (neat): 3444, 2927, 2856,
2677, 1724, 1664, 1633, 1566, 1543, 1518, 1458, 1406, 1367, 1333, 1248, 1203, 1161,
1115, 1088, 1010, 972, 928, 866, 802, 492, 434 cm–1. 1H NMR (300 MHz, CDCl3): δ = 2.69 (d,
CH3). 13C NMR (126 MHz, Acetone-d6): δ = 206.4 (m, C7), 29.6 (m, C8), other signals are
undetectable due to broadening. 19F NMR (282 MHz, CDCl3): δ = –133.6 (m, J (F3,F4) ≈ 23
Hz, J (F3,F6) ≈ 15 Hz, J (F3,F5) ≈ 8 Hz, 1 F, F3), –143.2 (m, J (F5,F4) = 22 Hz, J (F5,F6) = 20.3 Hz,
J (F5,F3) = 8.3 Hz, 1 F, F5); –160.6 (m, J (F6,F5) = 20.3 Hz, J (F6,F3) = 14.9 Hz, J (F6,F4) = 4.7 Hz,
1 F, F6); –168.2 (m, J (F4,F3) = 24.0 Hz, J (F4,F5) = 21.9 Hz, J (F4,F6) = 4.7 Hz, 1 F, F4).
HRMS (EI): m/z [M]+ calcd for C8H4F4O2: 208.0142; found: 208.0145.
1-(4,5-Difluoro-2-hydroxy-3-iodophenyl)ethanone (3g)
White solid; yield: 0.18 g (60%); Rf = 0.55 (hexane, twice); mp 117.9 – 119.7 °C. IR (KBr):
3442, 3103, 2927, 1749, 1647, 1614, 1568, 1481, 1421, 1369, 1306, 1219, 1199, 1172,
1
1059, 1024, 964, 889, 877, 829, 737, 673, 575 cm–1. H NMR (300 MHz, Acetone-d6): δ =
13.37 (s, 1 H, OH), 8.06 (t, J (H5,F4) ≈ J (H5,F3) = 9.4 Hz, 1 H, H5), 2.72 (s, 3 H, CH3). 13C NMR
(126 MHz, Acetone-d6): δ = 204.8 (s, C7), 160.7 (br. s, C1), 156.1 (dd, 1J (C3,F3) = 251.9 Hz, 2J
(C3,F4) = 15.0 Hz, C3), 143.6 (dm, 1J (C4,F4) = 242.4 Hz, 2J (C4,F3) = 16.1 Hz, C4), 119.9 (dm, 2J
2
(C5,F4) = 19.1 Hz, C5), 116.0 (m, C6), 75.9 (dm, J (C2,F3) = 22.9 Hz, C2), 27.0 (s, C8). 19F NMR
(282 MHz, Acetone-d6): δ = –103.4 (dd, J (F3,F4) = 24.4 Hz, J (F3,H5) = 8.9 Hz, 1 F, F3), –145.4
(br. s, 1 F, F4). HRMS (EI): m/z [M]+ calcd for C8H5F2IO2: 297.9297; found: 297.9294.
1-(2,3,4-Trifluoro-6-hydroxyphenyl)ethanone (3h)
Colorless oil; yield: 0.13 g (67%); Rf = 0.50 (hexane, twice). IR (neat): 3086, 2933, 2856,
1660, 1637, 1603, 1508, 1466, 1394, 1371, 1302, 1255, 1203, 1163, 1074, 1065, 1026, 964,
1
897, 812, 694, 677, 590, 551 cm–1. H NMR (300 MHz, CDCl3): δ = 12.72 (m, 1 H, OH), 6.56
(m, J (H6,F5) = 11.4 Hz, J (H6,F4) = 6.2 Hz, J (H6,F3) = 2.4 Hz,1 H, H6), 2.66 (d, J (H8,F3) = 7.2
Hz,3 H, H8). 13C NMR (126 MHz, CDCl3): δ = 201.4 (m, C7), 159.3 (m, C1), 155.6 (dm, 1J (C3,F3)
= 258.5 Hz, 2J (C3,F4) = 10.9 Hz, C3), 152.1 (dm, 1J (C5,F5) = 257.9 Hz, 2J (C5,F4) = 11.2 Hz, C5),
1
2
2
2
133.5 (dm, J (C4,F4) = 244.1 Hz, J (C4,F5) = 15.9 Hz, J (C4,F3) = 16.9 Hz, C4), 106.9 (dm, J
(C2,F3) = 11.3 Hz, C2), 101.7 (dm, 2J (C6,F5) = 19.9 Hz, C6), 31.9 (d, 2J (C8,F) = 10.5 Hz, C8).
19F NMR (282 MHz, CDCl3): δ = –123.2 (m, J (F5,F4) = 22.4 Hz, J (F5,H6) = 11.4 Hz, 1 F, F5), –
129.6 (m, J (F3,F4) = 21 Hz, J (F3,H8) = 7.2 Hz, J (F3,H6) = 2.4 Hz,1 F, F3), –172.6 (m, J (F4,F5) ≈
J (F4,F3) = 22.4 Hz, J (F4,H6) = 6.2 Hz, 1 F, F4). HRMS (EI): m/z [M]+ calcd for C8H5F3O2:
190.0236; found: 190.0236.
1-(2,3,4-Trifluoro-6-hydroxy-5-iodophenyl)ethanone (3i)
White solid; yield: 0.02 g (7%); Rf = 0.26 (hexane, twice); mp 39.8 – 44.0 °C. IR (KBr): 2929,
2856, 2781, 1649, 1626, 1581, 1475, 1460, 1369, 1311, 1290, 1234, 1196, 1086, 1070,

1
1028, 972, 916, 856, 756, 596 cm–1. H NMR (300 MHz, CDCl3): δ = 13.73 (s, 1 H, OH), 2.71
(d, J (H8,F5) = 7.4 Hz, 3 H, CH3). 13C NMR (126 MHz, CDCl3): δ = 201.2 (t, C7), 158.7 (m, C1),
1
2
1
2
155.8 (dm, J (C3,F3) = 254.2 Hz, J (C3,F4) = 11.8 Hz, C3), 152.5 (dm, J (C5,F5) = 258.7 Hz, J
(C5,F4) = 11.4 Hz, C5), 133.3 (dt, J (C4,F4) = 248.3 Hz, J (C4,F5) ≈ J (C4,F3) = 17.7 Hz, C4),
106.3 (dm, 2J (C6,F5) = 11.6 Hz, C6), 69.1 (dm, 2J (C2,F3) = 23.5 Hz, C6), 31.7 (d, J (C8,F5) = 10.8
Hz, C8). 19F NMR (282 MHz, CDCl3): δ = –101.2 (m, J (F3,F4) = 24.7 Hz, J (F3,F5) = 14.7 Hz, 1 F,
F3), –129.1 (m, J (F5,F4) = 22.4 Hz, J (F5,F3) = 14.7 Hz, J (F5,H8) = 7.4 Hz, 1 F, F5), –169.0 (dd, J
(F4,F3) = 24.7 Hz, J (F4,F5) = 22.4 Hz, 1 F, F4). HRMS (EI): m/z [M]+ calcd for C8H4F3IO2:
315.9203; found: 315.9202.
1
2
2
Interaction of triisopropilsilylacetylenes 2b and 3c with 4-fluorobenzaldehyde by
action of p-toluenesulfonic acid monohydrate in toluene; General Procedure
To a solution of acetylene 2b or 3c (1.0 mmol) in toluene (5 mL) in an ace pressure tube
under argon 4-fluorobenzaldehyde (0.62 g, 5.0 mmol), p-TSA monohydrate (0.57 g, 3.0
mmol), MgSO4 (0.60 g, 5.0 mmol) were added, and the flask was hermetically closed with a
screw cap. The mixture was heated at 150 C for 14÷16 h with stirring. The mixture was
allowed to cool to room temperature, placed directly onto a chromatography plates (silica
gel) and air-dried. The target products were isolated by TLC using the mixture of hexane
and EtOAc as an eluent.
5,6-Difluoro-3-(4-fluorobenzylidene)-2-(4-fluorophenyl)-8-((E)-3-(4-
fluorophenyl)acryloyl)chroman-4-one (4)
Yellow solid; yield: 0.47 g (88%); Rf = 0.20 (EtOAc/hexane, 1:7, 3 times); mp 65.1 °C
(decomp.). IR (KBr): 3070, 1711, 1676, 1658, 1601, 1508, 1471, 1448, 1415, 1334, 1277,
1234, 1196, 1176, 1159, 1118, 1097, 997, 974, 862, 833, 808, 771, 727, 636, 569, 507 cm–1.
1H NMR (300 MHz, CDCl3): δ = 8.06 (s, 1 H, H14), 7.82 (t, J (H21,H23) = 8.9 Hz, 1 H, H21), 7.46
(m, 2 H, H16), 7.35 (m, 2 H, H23), 7.19 – 6.84 (m, 10 H, 2H11 + H5 +2H24 +2H17 +2H12 + H20),
1
6.55 (s, 1 H, H9). 13C NMR (126 MHz, CDCl3): δ = 187.8 (s, C19), 180.0 (s, C7), 164.4 (d, J
(C25,F25) = 253.9 Hz, C25), 163.5 (d, 1J (C18,F18) = 253.2 Hz, C18), 163.0 (d, 1J (C13,F13) = 249.7
3
1
2
Hz, C13), 152.2 (d, J (C1,F3) = 7.2 Hz, C1), 146.4 (s, C20), 145.8 (dd, J (C4,F4) = 248.6 Hz, J
(C4,F3) = 13.7 Hz, C4), 139.9 (s, C14), 132.4 (d, C10), 132.0 (d, 3J (C11,F13) = 8.7 Hz, C11), 130.7
(d, J (C23,F25) = 8.7 Hz, C23), 130.0 (s, C8), 129.8 (d, C15), 129.6 (d, J (C16,F18) = 8.5 Hz, C16),
3
3
129.4 (d, C22), 126.7 (d, C21), 120.2 (d, J (C6,F3) = 17.8 Hz, C6), 118.6 (t, J (C2,F4) = 3.1 Hz,
2
3
C2), 116.3 (d, J (C12,F13) = 21.8 Hz, C12), 116.2 (d, J (C24,F25) = 21.9 Hz, C24), 116.1 (d, J
2
2
2
(C17,F18) = 21.5 Hz, C17), 115.9 (dd, J (C5,F4) = 20 Hz, C5), 78.2 (s, C9). 19F NMR (282 MHz,
2
CDCl3): δ = –108.4 (m, J (F25,H24) = 13.7 Hz, J (F25,H23) = 8.4 Hz, 1 F, F25), –109.5 (m, J
(F13,H12) = 13.5 Hz, J (F13,H11) = 8.3 Hz, 1 F, F13), –112.6 (m, J (F18,H17) = 13.5 Hz, J (F18,H16)
= 8.5 Hz, 1 F, F18), –127.5 (dd, J (F3,F4) = 23.0 Hz, J (F3,H5) = 8.8 Hz, 1 F, F3), –143.9 (dd, J
(F4,H5) = 23.0 Hz, J (F4,H5) = 9.8 Hz, 1 F, F4). HRMS (EI): m/z [M]+ calcd for C31H17F5O3:
532.1092; found: 532.1095.
6,8-Difluoro-3-(4-fluorobenzylidene)-2-(4-fluorophenyl)chroman-4-one (5)

Yellow solid; yield: 0.27 g (72%); Rf = 0.70 (EtOAc/hexane, 1:10, twice); mp 112.3 °C
(decomp.). IR (KBr): 3095, 3078, 2943, 2866, 1678, 1601, 1510, 1487, 1412, 1356, 1329,
1306, 1288, 1242, 1184, 1161, 1120, 1099, 1047, 1003, 987, 922, 885, 854, 833, 808, 769,
1
742, 673, 596, 573, 511, 490, 415 cm–1. H NMR (500 MHz, CDCl3): δ = 8.06 (s, 1 H, H14),
7.43 (m, 2 H, H16), 7.35 (ddd, J (H3,F4) = 8.1 Hz, J (H3,F6) = 3.1 Hz, J (H3,H5) = 3.0 Hz, 1 H, H3),
7.23 (m, 2 H, H11), 7.06 – 7.00 (m, 4 H, 2H12 + 2H17), 6.96 (ddd, J (H5,F6) = 10.0 Hz, J (H5,F4) =
8.0 Hz, J (H5,H3) = 3.0 Hz, 1 H, H5), 6.62 (s, 1 H, H9). 13C NMR (126 MHz, CDCl3): δ = 180.4
1
1
(dd, C7), 163.6 (d, J (C18,F18) = 253.1 Hz, C18), 163.0 (d, J (C13,F13) = 249.2 Hz, C13), 156.1
(dd, 1J (C4,F4) = 245.1 Hz, 3J (C4,F6) = 9.7 Hz, C4), 151.9 (dd, 1J (C6,F6) = 252.5 Hz, 3J (C6,F4) =
11.1 Hz, C6), 143.3 (dd, J (C1,F6) = 11.8 Hz, C1), 139.7 (s, C14), 132.7 (d, C10), 132.0 (d, J
2
3
(C11,F13) = 8.6 Hz, C11), 130.8 (d, C8), 129.6 (d, C15), 129.2 (d, 3J (C16,F18) = 8.5 Hz, C16), 123.8
(dd, J (C2,F4) = 7.8 Hz, C2), 116.2 (d, J (C12,F13) = 21.9 Hz, C12), 116.1 (d, J (C17,F18) = 21.7
3
2
2
Hz, C17), 110.7 (dd, J (C5,F4) = 27.9 Hz, J (C5,F6) = 21.3 Hz, C5), 107.9 (dd, J (C3,F4) = 23.4
Hz, C3), 77.6 (s, C9). 19F NMR (282 MHz, CDCl3): δ = –109.7 (m, J (F13,H12) = 13.7 Hz, J
(F13,H11) = 8.4 Hz, 1 F, F13), –113.1 (m, J (F18,H17) = 13.6 Hz, J (F18,H16) = 8.6 Hz, 1 F, F18), –
118.4 (td, J (F4,H3) ≈ J (F4,H5) = 8.0 Hz, J (F4,F6) = 3.0 Hz, 1 F, F4), –131.6 (ddd, J (F6,H5) =
10.0 Hz, J (F6,H3) = 3.1 Hz, J (F6,F4) = 3.0 Hz, 1 F, F6). HRMS (EI): m/z [M]+ calcd for
C22H12F4O2: 384.0768; found: 384.0758.
2
2
2
6,8-Difluoro-2-(4-fluorophenyl)chroman-4-one (6)
Yellow oil; yield: 0.05 g (18%); Rf = 0.28 (EtOAc/hexane, 1:10, twice). IR (thin): 3458, 2943,
2893, 2866, 1703, 1630, 1601, 1510, 1489, 1466, 1383, 1354, 1286, 1236, 1178, 1159,
1
1101, 1061, 995, 918, 883, 806, 679, 557, 499, 461 cm–1. H NMR (300 MHz, CDCl3): δ =
7.44 (m, 2 H, H11), 7.38 (ddd, J (H3,F4) = 7.9 Hz, J (H3,H5) = 3.0 Hz, J (H3,F6) = 2 Hz, 1 H, H3),
7.13 – 7.06 (m, 3 H, 2H12 + H5), 5.50 (dd, J (H9,H8’) = 12.8 Hz, J (H9,H8) = 3.2 Hz, 1 H, H9), 3.09
(dd, J (H8’,H8) = 17.1 Hz, J (H8’,H9) = 12.8 Hz, 1 H, H8’), 2.93 (dd, J (H8,H8’) = 17.1 Hz, J (H8,H9)
= 3.2 Hz, 1 H, H8). 13C NMR (126 MHz, CDCl3): δ = 191.2 (t, C7), 164.4 (d, 1J (C13,F13) = 248.3
Hz, C13), 157.3 (dd, 1J (C4,F4) = 245.2 Hz, 3J (C4,F6) = 9.5 Hz, C4), 153.2 (dd, 1J (C6,F6) = 253.5
3
2
3
Hz, J (C6,F4) = 11.1 Hz, C6), 147.9 (dd, J (C1,F6) = 11.8 Hz, C1), 135.0 (d, C10), 129.4 (d, J
(C11,F13) = 8.4 Hz, C11), 124.0 (dd, 3J (C2,F4) = 7.5 Hz, C2), 117.3 (d, 2J (C12,F13) = 21.8 Hz, C12),
112.5 (dd, J (C5,F4) = 27.9 Hz, J (C5,F6) = 21.3 Hz, C5), 108.8 (dd, J (C3,F4) = 23.1 Hz, C3),
81.1 (s, C9), 45.8 (d, C8). 19F NMR (282 MHz, CDCl3): δ = –110.5 (m, J (F13,H12) = 13.7 Hz, J
(F13,H11) = 8.5 Hz, 1 F, F13), –116.0 (td, J (F4,H3) ≈ J (F4,H5) = 7.9 Hz, J (F4,F6) = 3.1 Hz, 1 F,
F4), –127.2 (ddd, J (F6,H5) = 10.0 Hz, J (F6,F4) = 3.1 Hz, J (F6,H3) = 2 Hz, 1 F, F6). HRMS (EI):
m/z [M]+ calcd for C15H9F3O2: 278.0549; found: 278.0551.
2
2
2
Acknowledgment
The authors thank the Russian Foundation for Basic Research (grant № 19-53-
53003) and NSFC (grant № 21911530097) for financial support and the Chemical Service
Center SB RAS for spectral and analytical measurements.

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