Transformation of fluorinated 2-alkynylanilines by various catalytic systems

Article abstract of DOI:10.1016/j.jfluchem.2019.109394

Simple and efficient approaches to the synthesis of fluorinated benzoazaheterocycles with good yields are reported. Firstly a series of polyfluorinated 2-alkynylanilines – the versatile building blocks – was synthesized by the Sonogashira reaction of o-iodoaniline with terminal alkynes. Then the transformations of the obtained 2,3,4-trifluo-6-alkynilanilines in the presence of KOH or PdCl₂ in MeCN, and in the presence of monohydrate of p-toluenesulfonic acid (p-TSA?H₂O) in MeOH, EtOH or benzene were investigated. It was found that Ph- and n-Bu-containing alkynylanilines by action of PdCl₂ in MeCN underwent an intramolecular cyclization reaction to produce the corresponding indoles in high yields. The reaction of KOH with alkynes containing the tertiary alcohol function at the triple bond produced the unsubstituted on the pyrrole ring indole. It was found that fluorinated 2-alkynilanilines can be transformated into indoles, 2-arylketones and 2,3-dihydroquinolines by action of p-TSA?H₂O in boiling alcohols, depending on the substituent at the triple bond. The use of benzene as a solvent in the reaction of p-TSA?H₂O with polyfluorinated alkynes, bearing an alcohol group resulted in representative series of 2,3-dihydroquinolinones containing a substituents R¹ and R² in the 2nd position of their structure (R = H, H; Me, Me; H, i-Pr; H, Ph).

Full text of DOI:10.1016/j.jfluchem.2019.109394

Journal Pre-proof
Transformation of fluorinated 2-alkynylanilines by various catalytic
systems
Larisa Politanskaya, Maxim Petyuk, Evgeny Tretyakov
PII:
S0022-1139(19)30318-5
DOI:
https://doi.org/10.1016/j.jfluchem.2019.109394
FLUOR 109394
Reference:
To appear in:
Journal of Fluorine Chemistry
Received Date:
Revised Date:
Accepted Date:
10 September 2019
9 October 2019
10 October 2019
Please cite this article as: Politanskaya L, Petyuk M, Tretyakov E, Transformation of
fluorinated 2-alkynylanilines by various catalytic systems, Journal of Fluorine Chemistry
(2019), doi: https://doi.org/10.1016/j.jfluchem.2019.109394
This is a PDF file of an article that has undergone enhancements after acceptance, such as
the addition of a cover page and metadata, and formatting for readability, but it is not yet the
definitive version of record. This version will undergo additional copyediting, typesetting and
review before it is published in its final form, but we are providing this version to give early
visibility of the article. Please note that, during the production process, errors may be
discovered which could affect the content, and all legal disclaimers that apply to the journal
pertain.
© 2019 Published by Elsevier.

Transformation of fluorinated 2-alkynylanilines by various catalytic
systems
Larisa Politanskayaa,b,* , Maxim Petyukb, Evgeny Tretyakova,b
[a]
[b]
N.N. Vorozhtsov Institute of Organic Chemistry, Siberian Branch of Russian Academy of Sciences
Ac. Lavrentiev Ave. 9, Novosibirsk 630090, Russian Federation
Novosibirsk State University, Pirogova Str. 2, Novosibirsk 630090, Russian Federation
 Corresponding author. Tel.: +7-383-330-6859; fax: +7-383-330-9752; e-mail: plv@nioch.nsc.ru
Graphical abstract
____________________________________________________________________________________
Highlights
 Catalytic modification of 2-alkynylanilines into 5-and 6-member azaheterocycles
 Selective p-TSAH2O - induced one pot hydration – cyclisation process in
benzene
 Efficient synthesis of fluorinated 2-R-indoles by action of PdCl2 in MeCN
A B S T R A C T
Simple and efficient approaches to the synthesis of fluorinated benzoazaheterocycles with good
yields are reported. Firstly a series of polyfluorinated 2-alkynylanilines – the versatile building
1

blocks – was synthesized by the Sonogashira reaction of o-iodoaniline with terminal alkynes.
Then the transformations of the obtained 2,3,4-trifluo-6-alkynilanilines in the presence of KOH
or PdCl2 in MeCN, and in the presence of monohydrate of p-toluenesulfonic acid (p-TSAH2O)
in MeOH, EtOH or benzene were investigated. It was found that Ph- and n-Bu-containing
alkynylanilines by action of PdCl2 in MeCN underwent an intramolecular cyclization reaction to
produce the corresponding indoles in high yields. The reaction of KOH with alkynes containing
the tertiary alcohol function at the triple bond produced the unsubstituted on the pyrrole ring
indole. It was found that flu
orinated 2-alkynilanilines can be transformated into indoles, 2-arylketones and 2,3-
dihydroquinolines by action of p-TSAH2O in boiling alcohols, depending on the substituent at
the triple bond. The use of benzene as a solvent in the reaction of p-TSAH2O with
polyfluorinated alkynes, bearing an alcohol group resulted in representative series of 2,3-
dihydroquinolinones containing a substituents R1 and R2 in the 2nd position of their structure (R
= H, H; Me, Me; H, i-Pr; H, Ph).
Keywords Cross-coupling, fluorinated alkynes, triple bond hydration, fluorinated heterocycles,
2,3-dihydroquinolinones
1. Introduction
Fluorine-containing compounds are interesting to organic chemists because they have found
a wide range of applications in pharmaceuticals, medicine, agrochemicals, and materials science.
The efforts of researchers are directed at finding new synthetic strategies for fluorine
incorporation into organic molecules [1] and at demonstrating the unique ability of fluorine to
modulate their structural, physical, and biological properties [2].
Functionalisation of alkynes is a fundamental and important class of reaction in organic
synthesis. Alkynes have been extensively used as important building blocks and versatile
precursors in synthesis of many important products [3–6] such as alkenes [7], alcohols [8–10],
amines [10], -amino ketones [11], 1,2-diketones [12], amides [13], nitriles [14], cyclic acetals
[15], ynamides [16], enynes [17], ketones [18–20], arene derivatives and heterocycles [4,21].
Among these important applications, hydration and heterocyclisation of 2-akynylanilines are
practical and atom-economical methods for the synthesis of ketones and azaheterocycles, which
are basic reactions in alkyne chemistry. The use of fluorinated compounds in these reactions
opens up broad prospects for obtaining practically valuable potentially biologically active
substances [22–29].
In this regard, the synthesis of new polyfluorinated arylacetylenes and the search for
effective reaction systems for their transformation into potentially biologically active compounds
is a worthwhile research task. The aim of our work is to study the behavior of fluorinated 2-
alkynylanilines under the action of a transition metal salt (PdCl2) as well as under alkaline
conditions (KOH) and acid catalysis (p-TSAH2O) to develop effective approaches to the
synthesis of azaheterocycles.
2. Results and discussion
2

2.1. The synthesis of the starting compounds
At the first stage 2,3,4-trifluoro-6-iodoaniline (1) [22] was cross-coupled with acetylenes 2a-
e in MeCN in the presence of Pd(PPh3)2Cl2 (5 mol %), CuI (10 mol %) and Et3N as the catalysts
to obtain 2-alkynylanilines 3a–e in 7899% yields (Scheme 1) by analogy with the previously
described procedure [30].
Scheme 1. Synthesis of polyfluorinated arylacetylenes 3a–e.
In addition, 6-ethynyl-2,3,4-trifluoroaniline (3g) was synthesized as described in the
literature [22,31] with some modifications. The cross-coupling reaction of iodaniline 1 with
trimethylsilylacetylene 2f was carried out in a similar catalytic system in triethylamine as a
solvent at room temperature for 72 h and led to the formation of the previously known [22] silyl
derivative 3f (Scheme 2). The crude product was next introduced into the reaction with K2CO3 in
methanol solution at r.t. to obtain the desired ethynylaniline 3g (Scheme 2).
Scheme 2. Synthesis of polyfluorinated arylacetylene 3g.
Prepared 2-alkynylanilines 3a–g, as base compounds, were then subjected to various
transformations under different reaction conditions, in accordance with the aim of this study.
2.2. Analysis of the reactivity of 2-alkynylanilines in the presence of PdCl2
Interaction of compounds 3 with transition metal salt (PdCl2) was implemented by
refluxing in an acetonitrile solution according to a previously reported method [27]. It was found
that 2-alkynylanilins 3a and 3b are transformed into the corresponding indoles 4a and 4b within
1 h (Scheme 3). 5,6,7-Trifluoro-2-phenyl-1H-indole (4a) and 5,6,7-trifluoro-2-butyl-1H-indole
(4b) were isolated by thin-layer chromatography (TLC) in 96% and 99% yields, respectively. In
contrast, the use of the PdCl2/MeCN catalytic system with compounds 3c–e,g was not effective.
3

In these cases, the formation of multicomponent mixtures of products was observed, the
separation of which by the TLC method was not successful (Scheme 3). It should be noted that
conversion degrees of starting 2-alkynylanilines 3 in all cases were 100%. The results of our
experiments are in good agreement with the literature data on the effect of transition metal salts
on the cyclization process: the formation of a complex mixture was observed by action of PtCl4
on o-alkynylanilines containing primary alcohol function [32].
Scheme 3. Reactivity of polyfluorinated arylacetylenes 3 by action of PdCl2 in MeCN.
Thus, it was found that arylacetylenes 3 with phenyl (a) and butyl (b) fragments at the
triple bond become selectively transformed to the corresponding indoles by action of PdCl2 in
boiling acetonitrile, whereas other studied substrates gave a range of products with unidentified
structure.
2.3. Evaluation of the reactivity of 2-alkynylanilines in the presence of KOH
At the next stage the reactions behavior of 3 in an alkaline medium was investigated. It was
shown that reflux of arylacetylene 3a in acetonitrile solution with 3 equivalents of KOH leads to
obtaining of indole 4a in 73% yield (Scheme 4). The required reaction time was 14 h. The
reactions were terminated after disappearance of 19F NMR signals belonging to 3 in the reaction
mixture.
Scheme 4. Reactivity of polyfluorinated arylacetylenes 3 by action of KOH in MeCN.
4

Arylacetylene 3b underwent a similar transformation within 9 h. Indole 4b was isolated
by TLC in 86% yield (Scheme 4). The transformation of ethynylaniline 3g into indole 4g
(unsubstituted on the pyrrole ring) proceeded under the action of KOH with substantial
thickening of the reaction mass, resulting in a low yield of the reaction product. It is possible that
the additional cause of this low yield of 4g is the high volatility of this compound. In the case of
reaction of compound 3c with KOH, no individual products could be isolated from the reaction
mixture (Scheme 4).
Arylacetylene 3e in the presence of KOH in MeCN medium gave (besides indole 4e,
supposedly) indole 4g unsubstituted on the pyrrole ring (Scheme 5). The precursor of 4g is most
likely arylacetylene 3g, derived from the starting aniline 3e via the retro-Favorsky reaction. The
formation of 2-ethynylanilines has been observed previously in the reaction of polyfluorinated
analogs of arylacetylene 3e in boiling benzene [30] and MeCN [26] in the presence of KOH
earlier.
Scheme 5. Reactivity of arylacetylene 3e in MeCN in the presence of KOH.
Thus, it was found that polyfluorinated arylacetylenes 3a,b,e,g are converted in the
presence of KOH into indoles. Isolation of reaction products of primary carbinol 3c was not
successful. In the case of the tertiary carbinol 3e, the reaction system based on KOH may be used
to obtain indole 4g unsubstituted on the pyrrole ring.
2.4. Investigation of the reactivity of 2-alkynylanilines under the action of p-TSAH2O in the
aliphatic alcohols and benzene medium
Then we turned to the analysis of the acidic catalytic system, namely, the use of p-toluene
sulfonic acid monohydrate in boiling ethanol. It was found that alkynes 3a and 3b by action of
two equivalents of p-TSAH2O in EtOH for 15 h form the same heterocyclization products 4a
and 4b as in the case of PdCl2 and KOH in MeCN (Scheme 6).
Scheme 6. Reactivity of polyfluorinated arylacetylenes 3a,b in EtOH in the presence of p-
TSAH2O.
5

In the case of compound 3c, the reaction initiated by p-TSAH2O in EtOH led to the
formation of indole 4h (R = CH2OEt) isolated in 37% yield. Nevertheless, this was not the only
product of 2-alkynylaniline transformation. There was also the formation of ketone 5h as a result
of the triple bond hydration reaction in compound 3c. In addition, all reaction products with the
19
help of the solvent (EtOH) were transformed into ethers (Scheme 7). In the F NMR spectrum
of the reaction mixture, the molar ratio of the products 4h and 5h was 1.7 : 1.
Scheme 7. Reactivity of 3c by action of p-TSAH2O in EtOH and MeOH.
When methanol was used as a solvent (instead of ethanol) in the reaction of 3c with p-
TSAH2O the qualitative composition of the reaction products remained the same, but the ratio
of indole to ketone changed to the opposite : from 1.7 : 1 to 1 : 2. As a result, corresponding
indole 4i (R = CH2OMe) and ketone 5i were isolated in 18% and 33% yields, respectively
(Scheme 7).
Thus, it was found that the change in the polarity of the solvent affects the ratio of the
rates of competing reactions (cyclization and hydration of triple bond). This conclusion is
consistent with the literature data [28].
The interaction of 3e with p-TSAH2O in boiling ethanol led to the formation of indole 4j
and the cyclic product 2,2-dimethyl-2,3-dihydroquinoline-4(1H)-one 6e, which is a consequence
of the triple bond hydration reaction (Scheme 8). A precursor of indole 4j, apparently, was
indole 4e, which was observed in the 19F NMR spectra of the reaction mass, but failed to be
isolated by chromatography. The molar ratio of 4e : 4j : 6e in the reaction mass was 1 : 5 : 7.5.
Reaction products 4j and 6e were isolated in 14% end 39% yields, respectively (Scheme 8).
Scheme 8. Reactivity of 3e by action of p-TSAH2O in EtOH.
6

Alkyne 3d showed an even greater propensity (in comparison with 3e) for hydration of
the triple bond by action of p-TSAH2O in boiling ethanol: after 25 h it was completely
transformed into 2,3-dihydroquinolinones 6d and was isolated in a 85% yield (Scheme 9).
Scheme 9. Reactivity of 3d under the action of p-TSAH2O in EtOH.
Thus, alkynes 3 in the presence of p-TSAH2O in boiling alcohols can be converted into
indoles 4, 2-arylketones 5, and 2,3-dihydroquinolinones 6, depending on the substituent R at the
triple bond. For substrates with Ph and n-Bu groups (R), indoles were obtained as stand-alone
products, whereas for alkynes containing an alcohol function in the substituent (R = C(CH3)2OH,
CH2OH and CH(OH)CH(CH3)2), triple bond hydration products were also observed.
Further analysis of the reactivity of alkynes 3 in the presence of p-TSAH2O was
carried out in a solution of benzene, which is a less polar media than aliphatic alcohols. It was
found that arylacetylene 3a by action of p-TSAH2O in boiling benzene underwent an
intramolecular cyclization reaction with the formation of indole 4a (Scheme 10).
Scheme 10. Reactivity of 3a by action of p-TSAH2O in benzene.
In the case of arylacetylenes 3d and 3e, the reaction proceeded along the path of
formation of 2,3-dihydroquinolinones 6d and 6e, isolated by TLC in 81 and 75% yields,
respectively (Scheme 11). According to the 19F NMR spectra of the reaction mixtures,
7

byproducts containing an indole framework were present only in trace amounts. Therefore, the
replacement of the alcohol with benzene as a solvent led to that the formation of cyclic ketones
became the predominant direction of the hydration reaction. This statement is especially clearly
confirmed by the transformation of arylacetylene 3c by p-TSAH2O into 2,3-dihydroquinolinone
6c in benzene (Scheme 11). It is noteworthy that in ethyl and methyl alcohols, 3c reacted with p-
TSAH2O thereby producing a mixture of indoles 4 and acyclic ketones 5 (Scheme 7). The yield
of the product 6c (R1, R2 = H) is less than that for 6d (R1 = H; R2 = i-Pr) and 6e (R1, R2 = Me).
However, product 6c was not obtained at all when we varied the reaction conditions and used
other solvents such as dioxane, dichloroethane, methylene chloride or lowered the reaction
temperature.
Scheme 11. Reactivity of 3c–e by action of p-TSAH2O in benzene.
Thus, the use of benzene as a solvent instead of aliphatic alcohol in the reaction of
alkynes containing an alcohol group with p-TSAH2O is more appropriate to produce 2,3-
dihydroquinolinones 6.
To study the scope of this method of 2,3-dihydroquinolinones synthesis, we expanded the
range of fluorinated alkynes introduced into these reaction, and also investigated the reactivity of
their non-fluorinated analog. We also replaced one of the substituents at the triple bond of alkyne
on the aromatic fragment (R = Ph).
2.5. The synthesis of the 2,3-dihydroquinolines from 2-alkynylanilines containing an alcohol
group in the substituent at the triple bond by action of p-TSAH2O in benzene
The starting materials for this study (a representative series of 2-alkynylanilines 8a–i with
different fluorine contents) were prepared via the Sonogashira cross-coupling of o-iodoanilines 1
and 7a–e [30] with terminal acetylenes containing an alcohol function (Table 1). Target
compounds were obtained in good to excellent yields. Further, the triple bond in arylacetylenes 8
was subjected to a hydration reaction by action of p-TSAH2O in benzene (Table 2).
Table 1. Synthesis of 2-alkynylanilines 8.
8

Entry Iodoaniline 7 Arylacetylene 8
Yield (%)
1
75
2
3
96
68
4
5
6
7
8
9
93
94
60
85
84
98
9

Table 2. Synthesis of 2,3-dihydroquinolinones 9.
Entry Arylacetylene 8
2,3-Dihydroquinolinone 9 Yield (%)
1
10
2
3
4
5
6
7
8
67
9
90
14
85
15
89
10

9
54
From the data of Table 2 it follows that the reaction products in all cases were exclusively
2,3-dihydroquinolinones. That means, the proposed approach can be considered as universal and
applied to both fluorinated and non-fluorinated substrates. However, the yields of products,
unsubstituted at the 2 position are extremely low due to the considerable thickening of the
reaction mass (Table 2, entries 1,3,5,7).
The proposed mechanism of the 2,3-dihydroquinolinones 6 and 9 formation (Scheme 12)
includes a sequence of hydration, dehydration, and intramolecular cyclization reactions that is
consistent with the literature data [25]. It is obvious that R1 and R2 = Ph and Alk facilitate the
reaction, due to the stabilization of the carbocation in compared with R1 = R2 = H.
Scheme 12. The proposed mechanism of 2,3-dihydroquinolinones formation in presence of p-
TSAH2O.
Thus, this method is poorly applicable to primary alcohols and for the effective synthesis
of 2,3-unsubstituted 2,3-dihydroquinolinones, it seems that preliminary structural modification
of substrates is necessary, for example, protection of the amino group [33].
Thus, we propose a simple and convenient one pot way to obtain 2-phenyl-substituted
2,3-dihydroquinolinones based on the corresponding alkynes transformation in presence of p-
TSAH2O in benzene. These compounds can not only be of independent value as potentially
biologically active substances, but also be precursors of more complex heterocyclic ensembles,
for example, derivatives of quinoline. Thus, we obtained a new polyfluorinated heterocycle 10,
which is a structural analogue of compounds that showed promising single-digit micromolar
antiproliferative potency toward human cancer cells [23].
Scheme 13. Synthesis of polyfluorinated azaheterocycle 10 from 2,3-dihydroquinolinone 9d and
1-(2-amino-3,4,5-trifluorophenyl)ethanone in presence of p-TSAH2O.
11

3. Conclusion
In summary, we described a simple and efficient protocols for the synthesis of
polyfluorinated 2,3-dihydroquinolinones and indoles: biologically important aza-heterocyclic
scaffolds. In the course of this study, we synthesized previously unknown fluorinated 2-
alkynylanilines and investigated their reactivity in different reaction systems. It was
demonstrated that in MeCN by action of PdCl2, the Ph- and n-Bu-containing 2-alkynylanilines
undergo the intramolecular cyclization reaction producing the corresponding indoles in high
yields. The reaction of substrate, containing the tertiary alcohol function in the substituent at the
triple bond, with KOH in MeCN was employed for the synthesis of a fluorinated indole
unsubstituted on the pyrrole ring. It was revealed that fluorinated 2-alkynylanilines are
transformed by p-TSAH2O into indoles, 2,3-dihydroquinolinones and 2-arylketones, depending
on the solvent and nature of substituent R at the triple bond. When benzene serves as a solvent in
the reaction of alcohol group-containing alkynes with p-TSAH2O, selective production of 2,3-
dihydroquinolinones is observed. So we have discovered a simple, convenient and universals one
pot method for synthesis of 2,3-dihydroquinolinones containing an alkyl or phenyl group in 2
position in good yields. The reaction system based on p-TSAH2O has a number of obvious
advantages. Accordingly, in terms of cost, it is much more economical than a palladium catalyst
and more environmentally friendly than potassium hydroxide. From the standpoint of synthetic
possibilities, this strategy enables to obtain not only indoles, but also cyclic and acyclic carbonyl
compounds.
4. Experimental section
4.1 General
All solvents were purified using standard procedures. Toluene was kept over CaH2 before
use. The starting 2,3,4-trifluoro-6-iodoaniline (1) was synthesized according to previously
described methods [22]. Other chemicals were obtained from commercial sources and were used
without further purification. Preparative TLC was performed on Merck precoated silica gel 60
PF254 containing gypsum. Visualization of the developed chromatograms was performed by UV
light. To obtain analytically pure samples, the solid synthesized compounds were crystallized
from hexane.
1
NMR spectra were recorded on a Bruker Avance-300 (300.13 MHz for H and 282.37
19
1
13
MHz for F) and DRX-500 (500.13 MHz for H, 125.76 MHz for C) spectrometers. CDCl3
and acetone-d6 were used as solvents, with residual CHCl3 (δH = 7.26) or CDCl3 (δC = 77.0) and
acetone (δH = 2.15) or acetone-d6 (δC = 28.6 and 205.0) being employed as internal standards.
19
13
C6F6 (δF = –163.0 ppm) was used as external reference for recording the F NMR spectra. C
NMR spectra were recorded with C–H spin decoupling. Masses of molecular ions were
12

determined by HRMS on a DFS Thermo scientific instrument (EI, 70 eV). Melting points were
recorded on a Mettler-Toledo FP81 Thermosystem apparatus. The IR spectra were recorded on a
Bruker Vector 22 spectrometer (KBr or thin film). The Raman spectra were recorded on
Ramanscope Senterra (25 mV, 785 nm).
The structures of all new polyfluorinated compounds 2–10 prepared here were
1
corroborated by their 19F, H and 13C NMR, high-resolution mass spectrometry, and IR-
spectroscopy data (see Supplementary data). Signals in the NMR spectra of 3–10 were assigned
on the basis of spin coupling constants that are typical for polyfluorinated arenes [22–309].
4.2. Synthetic procedures
4.2.1. 2-alkynylanilines 3a–e, 8a–j; general procedure
To a solution of iodoaniline 1, 7a-e (1 mmol) and acetylenes 2 (1.5 mmol) in dry MeCN (10
mL) in a Schlenk flask under argon were added Pd(PPh3)2Cl2 (28 mg, 0.04 mmol), CuI (17 mg,
0.09 mmol) and Et3N (3 mL). The reaction mixture was stirred at 60 °C for 3 h. Then, the
mixture was allowed to cool down to r.t., and CH2Cl2 (10 mL) was added. The mixture was
poured into H2O (20 mL) and extracted with CH2Cl2 (3 × 50 mL). The combined organic layers
were washed with H2O (20 mL) and dried (MgSO4). After evaporation of the solvent in vacuo,
the crude product was purified by preparative TLC to obtain 3.
4.2.1.1. 2,3,4-Trifluoro-6-(phenylethynyl)aniline (3a)
1
Yellowish solid; yield: 215 mg (86%); Rf = 0.70 (EtOAc/hexane, 1:10, twice); 19F, H NMR
spectra are similar to those published earlier [29].
4.2.1.2. 2,3,4-Trifluoro-6-(hex-1-ynyl)aniline (3b)
Yellowish oil; yield: 186 mg (82%); Rf = 0.80 (EtOAc/hexane, 1:10, twice); IR (thin): 3487,
3388, 2960, 2935, 2873, 2227, 1647, 1589, 1522, 1481, 1381, 1302, 1182, 1145, 1022, 955, 858,
712, 555 cm–1. 1H NMR (300 MHz, Acetone-d6):  = 6.91 (ddd, J (H3,F4) = 10.8 Hz, J (H3,F5) =
8.0 Hz, J (H3,F6) = 2.2 Hz, 1 H, H3), 4.94 (s, 2 H, H1), 2.46 (t, J (H9,H10) = 7.0 Hz, 2 H, H9),
13
1.62–1.39 (m, 4 H, H10 + H11), 0.91 (t, J (H12,H11) = 7.0 Hz, 3 H, H12). C NMR (125.8 MHz,
1
2
1
Acetone-d6):  = 142.9 (ddd, J (C4,F4) ≈ 240 Hz, J (C4,F5) = 10.9 Hz, C4), 141.1 (ddd, J
(C5,F5) = 247.7 Hz, 2J (C5,F6) = 16.5 Hz, 2J (C5,F4) = 13.3 Hz, C5), 140.4 (ddd, 1J (C6,F6) ≈ 240
Hz, 2J (C6,F5) = 12.1 Hz, C6), 136.5 (d, 2J (C1,F6) = 10.5 Hz, C1), 114.6 (dd, 2J (C3,F4) = 19.0 Hz,
3J (C3,F5) = 3.2 Hz, C3), 104.9 (m, C2), 98.1 (m, C7), 75.2 (m, C8), 31.6 (s, C9), 22.7 (s, C10), 19.6
(s, C11), 13.8 (s, C12). F NMR (282 MHz, Acetone-d6): δ = –152.0 (dd, J (F4,F5) = 21.4 Hz, J
19
(F4,H3) = 10.8 Hz, 1 F, F4), –155.6 (dt, J (F6,F5) = 19.5 Hz, J (F6,H3) = 2.2 Hz, 1 F, F6), –160.7
(m, J (F5,F4) = 21.4 Hz, J (F5,F6) = 19.5 Hz, J (F5,H3) = 8.0 Hz, 1 F, F5). HRMS (EI): m/z [M]+
calcd for C12H12F3N: 227.0916; found: 227.09017.
4.2.1.3. 3-(2-Amino-3,4,5-trifluorophenyl)prop-2-yn-1-ol (3c)
White solid; yield: 156 mg (78%); Rf = 0.45 (EtOAc/hexane, 1:5, 4 times); mp 97.9–99.2 °C. IR
(KBr): 3396, 3315, 3207, 2227, 1645, 1618, 1524, 1485, 1360, 1308, 1182, 1149, 1014, 978,
870, 850, 715, 588, 472, 445 cm–1. 1H NMR (300 MHz, Acetone-d6):  = 6.99 (ddd, J (H3,F4) =
10.6 Hz, J (H3,F5) = 8.0 Hz, J (H3,F6) = 2.3 Hz, 1 H, H3), 5.18 (s, 2 H, H1), 4.44 (s, 2 H, H9),
13

13
1
2
3.00 (s, 1 H, OH). C NMR (125.8 MHz, Acetone-d6):  = 142.5 (ddd, J (C4,F4) = 235 Hz, J
(C4,F5) = 10.7 Hz, C4), 141.5 (ddd, 1J (C5,F5) = 248.3 Hz, 2J (C5,F6) = 16.6 Hz, 2J (C5,F4) = 13.5
Hz, C5), 140.1 (ddd, 1J (C6,F6) = 241.2 Hz, 2J (C6,F5) = 12.3 Hz, C6), 137.1 (d, 2J (C1,F6) = 10.7
2
3
Hz, C1), 114.6 (dd, J (C3,F4) = 19.0 Hz, J (C3,F5) = 3.2 Hz, C3), 103.4 (m, C2), 96.6 (m, C7),
78.7 (m, C8), 51.0 (s, C9). 19F NMR (282 MHz, Acetone-d6): δ = –152.1 (dd, J (F4,F5) = 21.4 Hz,
J (F4,H3) = 10.6 Hz, 1 F, F4), –155.5 (dm, J (F6,F5) = 19 Hz, J (F6,H3) = 2 Hz, 1 F, F6), –159.8
(td, J (F5,F4) ≈ J (F5,F6) = 21 Hz, J (F5,H3) = 8.0 Hz, 1 F, F5). HRMS (EI): m/z [M]+ calcd for
C9H6F3NO: 201.0396; found: 201.0395.
4.2.1.4. 1-(2-Amino-3,4,5-trifluorophenyl)-4-methylpent-1-yn-3-ol (3d)
Yellowish solid; yield: 240 mg (99%); Rf = 0.67 (EtOAc/hexane, 1:5); mp 46.8 °C (dec.). IR
(KBr): 3458, 3333, 2964, 2929, 2875, 2227, 1597, 1522, 1481, 1379, 1300, 1178, 1146, 1022,
991, 958, 854, 717, 638, 542 cm–1. 1H NMR (300 MHz, CDCl3):  = 6.82 (ddd, J (H3,F4) = 10.3
Hz, J (H3,F5) = 7.8 Hz, J (H3,F6) = 2.2 Hz, 1 H, H3), 4.39 (d, J (H9,H11) = 5.8 Hz, 1 H, H9), 4.23
(s, 2 H, H1), 3.21 (s, 1 H, H10), 1.93 (m, J (H11,H9) = 6 Hz, 1 H, H11), 1.01 (t, J (H12,H11) = 7.2
Hz, 6 H, H12). 13C NMR (125.8 MHz, CDCl3):  = 142.7 (ddd, 1J (C4,F4) = 237.3 Hz, 2J (C4,F5)
= 10.8 Hz, C4), 140.8 (ddd, 1J (C5,F5) = 251.8 Hz, 2J (C5,F6) = 16.5 Hz, 2J (C5,F4) = 13.3 Hz, C5),
1
2
2
139.9 (ddd, J (C6,F6) = 242.3 Hz, J (C6,F5) = 12.4 Hz, C6), 134.4 (dm, J (C1,F6) = 10.8 Hz,
C1), 113.9 (dd, J (C3,F4) = 19.2 Hz, J (C3,F5) = 3.4 Hz, C3), 102.7 (m, C2), 95.6 (m, C7), 79.2
(m, C8), 68.1 (s, C9), 34.4 (s, C10), 18.1 (s, C11), 17.4 (s, C11’). 19F NMR (282 MHz, CDCl3): δ =
–150.9 (dd, J (F4,F5) = 21.6 Hz, J (F4,H3) = 10.3 Hz, 1 F, F4), –156.2 (dd, J (F6,F5) = 19.7 Hz, J
(F6,H3) = 2.2 Hz, 1 F, F6), –159.3 (m, J (F5,F4) = 21.6 Hz, J (F5,F6) = 19.7 Hz, J (F5,H3) = 7.8
Hz, 1 F, F5). HRMS (EI): m/z [M]+ calcd for C12H12F3NO: 243.0866; found: 243.0868.
2
3
4.2.1.5. 4-(2-Amino-3,4,5-trifluorophenyl)-2-methylbut-3-yn-2-ol (3e)
Yellowish oil; yield: 187 mg (82%); Rf = 0.86 (EtOAc/hexane, 1:10, twice). IR (thin): 3361,
2983, 2935, 2222, 1649, 1593, 1522, 1483, 1379, 1365, 1279, 1230, 1165, 1124, 1020, 966, 931,
1
858, 694, 569 cm–1. H NMR (300 MHz, Acetone-d6):  = 6.96 (ddd, J (H3,F4) = 10.5 Hz, J
(H3,F5) = 8.0 Hz, J (H3,F6) = 2.2 Hz, 1 H, H3), 5.08 (s, 2 H, H1), 2.93 (s, 1 H, H8), 1.54 (t, 6 H,
H9). 13C NMR (125.8 MHz, Acetone-d6):  = 142.5 (ddd, 1J (C4,F4) = 235.8 Hz, 2J (C4,F5) = 10.7
Hz, C4), 141.2 (ddd, 1J (C5,F5) = 248.1 Hz, 2J (C5,F6) = 16.5 Hz, 2J (C5,F4) = 13.3 Hz, C5), 140.3
(ddd, 1J (C6,F6) = 240.9 Hz, 2J (C6,F5) = 12.2 Hz, C6), 136.6 (d, 2J (C1,F6) = 10.7 Hz, C1), 114.5
2
3
(dd, J (C3,F4) = 19.1 Hz, J (C3,F5) = 3.3 Hz, C3), 103.6 (m, C2), 102.8 (m, C7), 75.7 (m, C8),
65.2 (s, C9), 31.8 (s, C10). F NMR (282 MHz, Acetone-d6): δ = –152.2 (ddd, J (F4,F5) = 21.4
19
Hz, J (F4,H3) = 10.9 Hz, 1 F, F4), –155.6 (dt, J (F6,F5) = 19.1 Hz, J (F6,H3) = 2.2 Hz, 1 F, F6), –
160.7 (m, J (F5,F4) = 21 Hz, J (F5,F6) = 19 Hz, J (F5,H3) = 8.0 Hz, 1 F, F5). HRMS (EI): m/z [M]+
calcd for C11H10F3NO: 229.0709; found: 229.0708.
4.2.1.6. 3-(2-Aminophenyl)prop-2-yn-1-ol (8a)
Brown solid; yield: 110 mg (75%); Rf = 0.16 (EtOAc/hexane, 1:5, twice); mp 113.1 °C (dec.)
(48–49 °C [32]). IR (KBr): 3361, 2920, 2864, 2229, 1616, 1574, 1493, 1454, 1358, 1313, 1246,
1159, 1018, 953, 752, 553, 478 cm–1. 1H NMR (500 MHz, Acetone-d6):  = 7.14 (dm, J (H3,H4)
= 7.7 Hz, J (H3,H5) = 1.6 Hz, 1 H, H3), 7.03 (m, J (H5,H6) = 8.2 Hz, J (H5,H4) = 7.3 Hz, J
(H5,H3) = 1.6 Hz, 1 H, H5), 6.72 (dm, J (H6,H5) = 8.2 Hz, 1 H, H6), 6.53 (m, J (H4,H3) = 7.7 Hz,
14

13
J (H4,H5) = 7.3 Hz, 1 H, H4), 4.99 (s, 2 H, H1), 4.47 (s, 1 H, OH), 4.45 (s, 2 H, H9). C NMR
(125.8 MHz, Acetone-d6):  = 150.1 (s, C1), 132.4 (s, C3), 130.2 (s, C5), 117.1 (s, C4), 114.6 (s,
C6), 107.4 (s, C2), 94.4 (s, C7), 81.8 (s, C8), 51.1 (s, C9). HRMS (EI): m/z [M]+ calcd for
C9H9NO: 147.0679; found: 147.0680.
4.2.1.7. 3-(2-Aminophenyl)-1-phenylprop-2-yn-1-ol (8b)
Brown oil; yield: 214 mg (96%); Rf = 0.39 (EtOAc/hexane, 1:5, twice). IR (thin): 3454, 3373,
3063, 3032, 2873, 2218, 1701, 1614, 1574, 1493, 1454, 1313, 1261, 1190, 1159, 1036, 1014,
1
962, 918, 818, 752, 700, 638, 584, 553, 478 cm–1. H NMR (300 MHz, Acetone-d6):  = 7.64–
7.61 (m, 2 H, Hm), 7.40–7.27 (m, 3 H, Ho + Hp), 7.18 (dm, J (H3,H4) = 7.7 Hz, 1 H, H3), 7.06 (m,
J (H5,H6) = 8.2 Hz, J (H5,H4) = 7.3 Hz, 1 H, H5), 6.74 (dm, J (H6,H5) = 8.2 Hz, 1 H, H6), 6.55
(tm, J (H4,H3) ≈ J (H4,H5) = 7.5 Hz, 1 H, H4), 3.73 (s, 1 H, H9), 5.14 (s, 1 H, OH), 4.98 (s, 1 H,
H1). 1H NMR spectrum is close to that published earlier [32]. 13C NMR (100 MHz, Acetone-d6):
 = 150.3 (s, C1), 143.3 (s, C10), 132.5 (s, C3), 130.4 (s, C5), 129.1 (s, C12), 128.4 (s, C13), 127.4
(s, C11), 117.1 (s, C4), 114.7 (s, C6), 107.2 (s, C2), 96.3 (s, C7), 83.0 (s, C8), 64.9 (s, C9). HRMS
(EI): m/z [M]+ calcd for C15H13NO: 223.0992; found: 223.0990.
4.2.1.8. 3-(2-Amino-3,5-difluorophenyl)prop-2-yn-1-ol (8c)
Yellowish solid; yield: 124 mg (68%); Rf = 0.25 (EtOAc/hexane, 1:5, 4 times); mp 91.1 C (dec.).
IR (KBr): 3383, 3317, 3219, 3091, 2233, 1641, 1616, 1589, 1493, 1442, 1352, 1311, 1201, 1176,
1120, 1039, 1000, 967, 966, 854, 731, 584, 542, 432 cm–1. 1H NMR (300 MHz, Acetone-d6):  =
6.92 (m, J (H5,F6) = 11.5 Hz, J (H5,F4) = 9.0 Hz, J (H5,H3) = 2.9 Hz, 1 H, H5), 6.81 (dm, J
13
(H3,F4) = 9.0 Hz, J (H3,H5) = 2.9 Hz, 1 H, H3), 4.87 (s, 2 H, H1), 4.46 (s, 3 H, 2 H9 + OH). C
NMR (125.8 MHz, Acetone-d6):  = 153.7 (dd, 1J (C4,F4) = 234.8 Hz, 3J (C4,F6) = 12.4 Hz, C4),
151.0 (dd, 1J (C6,F6) = 240.6 Hz, 3J (C6,F4) = 12.9 Hz, C5), 135.6 (dd, 2J (C1,F6) = 13.7 Hz, C1),
113.6 (dd, 2J (C3,F4) = 23.3 Hz, C3), 109.6 (dd, 3J (C2,F4) = 11.0 Hz, C2), 105.1 (dd, 2J (C5,F6) =
19
27.1 Hz, 2J (C5,F4) = 23.0 Hz, C5), 96.9 (s, C7), 79.5 (m, C8), 51.0 (s, C9). F NMR (282 MHz,
Acetone-d6): δ = –156.3 (tm, J (F4,H5) ≈ J (F4,H3) = 9.0 Hz, 1 F, F4), –129.6 (dm, J (F6,H5) =
11.5 Hz, 1 F, F6). HRMS (EI): m/z [M]+ calcd for C9H7F2NO: 183.0490; found: 183.0494.
4.2.1.9. 3-(2-Amino-3,4,5-trifluorophenyl)-1-phenylprop-2-yn-1-ol (8d)
Yellowish solid; yield: 258 mg (93%); Rf = 0.27 (EtOAc/hexane, 1:7); mp 72.4–72.8 °C. IR
(KBr): 3415, 3334, 3280, 2835, 2231, 1601, 1523, 1475, 1379, 1304, 1286, 1257, 1200, 1145,
1036, 1009, 974, 920, 854, 742, 696, 646, 586, 557 cm–1. 1H NMR (300 MHz, CDCl3):  = 7.58
– 7.54 (m, 2 H, Hm), 7.43 – 7.32 (m, 3 H, Ho + Hp), 6.90 (m, J (H3,F4) = 10.2 Hz, J (H3,F5) = 7.7
13
Hz, J (H3,F6) = 2.3 Hz, 1 H, H3), 5.70 (d, 1 H, H9), 4.15 (s, 2 H, H1), 2.60 (d, 1 H, OH). C
1
2
NMR (125.8 MHz, CDCl3):  = 142.7 (ddd, J (C4,F4) = 239.8 Hz, J (C4,F5) = 10.8 Hz, C4),
141.0 (ddd, 1J (C5,F5) = 252.5 Hz, 2J (C5,F6) = 16.6 Hz, 2J (C5,F4) = 13.3 Hz, C5), 140.1 (s, C10),
139.9 (ddd, J (C6,F6) = 242.6 Hz, J (C6,F5) = 12.4 Hz, C6), 134.7 (dm, J (C1,F6) = 10.7 Hz,
C1), 128.7 (s, C12), 128.6 (s, C13), 126.4 (s, C11), 114.1 (dd, 2J (C3,F4) = 19.3 Hz, 3J (C3,F5) = 3.5
Hz, C3), 102.1 (m, C2), 95.5 (m, C7), 80.4 (m, C8), 65.0 (s, C9). 19F NMR (282 MHz, CDCl3): δ =
–147.7 (dd, J (F4,F5) = 21.6 Hz, J (F4,H3) = 10.2 Hz, 1 F, F4), –153.0 (dm, J (F6,F5) = 19.7 Hz, J
1
2
2
15

(F6,H3) = 2.3 Hz, 1 F, F6), –155.5 (m, J (F5,F4) = 21.6 Hz, J (F5,F6) = 19.7 Hz, J (F5,H3) = 7.7
Hz, 1 F, F5). HRMS (EI): m/z [M]+ calcd for C15H10F3NO: 277.0711; found: 277.0711.
4.2.1.10. 3-(2-Amino-3,5,6-trifluorophenyl)prop-2-yn-1-ol (8e)
Yellowish solid; yield: 189 mg (94%); Rf = 0.22 (EtOAc/hexane, 1:5, 5 times); mp 111.1–113.6
°C. IR (KBr): 3491, 3373, 3097, 2234, 1616, 1495, 1469, 1396, 1363, 1296, 1190, 1165, 1111,
1063, 1010, 914, 848, 723, 590, 503, 418 cm–1. 1H NMR (300 MHz, Acetone-d6):  = 7.13 (m, J
(H5,F4) ≈ J (H5,F6) = 10.7 Hz, J (H5,F3) = 7.3 Hz, 1 H, H5), 5.14 (s, 2 H, H1), 4.50 (s, 2 H, H9),
2.94 (s, 1 H, OH). 13C NMR (125.8 MHz, Acetone-d6):  = 147.7 (ddd, 1J (C3,F3) = 243.5 Hz, 2J
(C3,F4) = 13.7 Hz, C3), 145.9 (ddd, 1J (C6,F6) = 237.1 Hz, 3J (C6,F4) = 15.9 Hz, C6), 140.9 (ddd,
2
3
2
1J (C4,F4) = 235.6 Hz, J (C4,F3) = 13.9 Hz, J (C4,F6) = 12.5 Hz, C4), 136.2 (dm, J (C1,F6) =
15.2 Hz, C1), 106.1 (m, 2J (C5,F4) = 24.8 Hz, 2J (C5,F6) = 22.6 Hz, C5), 102.2 (m, C7), 103.4 (dm,
2J (C2,F3) = 17.7 Hz, C2), 73.5 (m, C8), 51.2 (s, C9). F NMR (282 MHz, Acetone-d6): δ = –
19
136.0 (m, J (F6,F3) = 13.8 Hz, J (F6,H5) = 11.0 Hz, J (F6,F4) = 3.2 Hz, 1 F, F6), –141.1 (m, J
(F3,F4) ≈ 21.4 Hz, J (F3,F6) = 13.5 Hz, J (F3,H5) = 7.3 Hz, 1 F, F3), –152.1 (ddd, J (F4,F3) = 21.8
Hz, J (F4,H5) = 10.6 Hz, J (F4,F6) = 3.2 Hz, 1 F, F4). HRMS (EI): m/z [M]+ calcd for C9H6F3NO:
201.0396; found: 201.0398.
4.2.1.11. 3-(2-Amino-3,5,6-trifluorophenyl)-1-phenylprop-2-yn-1-ol (8f)
Yellowish solid; yield: 166 mg (60%); Rf = 0.39 (EtOAc/hexane, 1:7, 5 times); mp 63.4 °C
(decomp.). IR (KBr): 3450, 3392, 3325, 3205, 2234, 1618, 1497, 1466, 1450, 1387, 1286, 1273,
1
1157, 1115, 1064, 1003, 920, 847, 739, 694, 646, 592, 553, 488 cm–1. H NMR (500 MHz,
CDCl3):  = 7.61–7.60 (m, 2 H, Hm), 7.42–7.34 (m, 3 H, Ho + Hp), 6.87 (m, J (H5,F4) ≈ J (H5,F6)
= 10.2 Hz, J (H5,F3) = 7.2 Hz, 1 H, H5), 5.76 (d, 1 H, OH), 4.11 (s, 2 H, H1), 2.36 (d, 1 H, H9).
13C NMR (125.8 MHz, CDCl3):  = 146.7 (ddd, 1J (C3,F3) = 247.4 Hz, 2J (C3,F4) = 13.9 Hz, C3),
144.8 (ddd, 1J (C6,F6) = 238.1 Hz, 3J (C6,F4) = 10.4 Hz, C6), 140.5 (ddd, 1J (C4,F4) = 239.6 Hz, 2J
(C4,F3) = 13.8 Hz, 3J (C4,F6) = 12.2 Hz, C4), 139.5 (s, C10), 133.1 (dm, 2J (C1,F6) = 15.2 Hz, C1),
2
2
128.4 (s, C12), 128.3 (s, C13), 126.1 (s, C11), 105.3 (m, J (C5,F4) ≈ J (C5,F6) = 23.9 Hz, C5),
100.4 (d, C7), 98.7 (dm, J (C2,F3) = 17.5 Hz, C2), 75.0 (m, C8), 64.8 (s, C9). F NMR (282
MHz, CDCl3): δ = –137.9 (m, J (F6,F3) = 13.4 Hz, J (F6,H5) = 10.5 Hz, J (F6,F4) = 2.5 Hz, 1 F,
F6), –141.3 (m, J (F3,F4) ≈ 21.4 Hz, J (F3,F6) = 13.4 Hz, J (F3,H5) = 7.1 Hz, 1 F, F3), –151.3 (ddd,
J (F4,F3) = 22.0 Hz, J (F4,H5) = 10.1 Hz, J (F4,F6) = 2.5 Hz, 1 F, F4). HRMS (EI): m/z [M]+ calcd
for C15H10F3NO: 277.0709; found: 277.0707.
2
19
4.2.1.12. 3-(2-Amino-3,4,5,6-tetrafluorophenyl)prop-2-yn-1-ol (8g)
Yellowish solid; yield: 186 mg (85%); Rf = 0.34 (EtOAc/hexane, 1:5, 3 times); mp 92.1 °C
(decomp.). IR (KBr): 3496, 3363, 3207, 2927, 2239, 1862, 1614, 1518, 1502, 1439, 1304, 1163,
1
1115, 1032, 997, 968, 827, 692, 578, 521 cm–1. H NMR (500 MHz, Acetone-d6): 5.48 (s, 2 H,
13
1
H1), 4.46 (s, 3 H, 2 H9 + OH). C NMR (125.8 MHz, Acetone-d6):  = 148.5 (dm, J (C3,F3) =
244.3 Hz, J (C3,F4) = 10.9 Hz, C3), 142.1 (dm, J (C5,F5) = 248.3 Hz, J (C5,F4) ≈ J (C5,F6) =
2
1
2
2
13.4 Hz, C5), 136.5 (dm, 2J (C1,F6) = 11.7 Hz, C1), 136.4 (dm, 1J (C6,F6) = 237.7 Hz, 2J (C6,F5) =
12.4 Hz, C6), 132.2 (dm, J (C4,F4) = 237.6 Hz, J (C4,F3) = 16.6 Hz, J (C4,F5) = 13.4 Hz, C4),
1
2
2
102.0 (m, C7), 94.0 (dm, J (C2,F3) = 17.9 Hz, C2), 72.3 (m, C8), 51.1 (s, C9). F NMR (282
2
19
16

MHz, Acetone-d6): δ = –139.2 (dm, J (F3,F4) = 22.0 Hz, J (F3,F6) = 9.3 Hz, J (F3,F5) ≈ 2 Hz, 1 F,
F3), –157.7 (m, J (F5,F4) = 21.6 Hz, J (F5,F6) ≈ 19.5 Hz, J (F5,F3) = 2 Hz, 1 F, F5), –162.3 (m, J
(F6,F5) = 19.9 Hz, J (F6,F3) = 9.3 Hz, J (F6,F4) = 6.9 Hz, 1 F, F6), –176.0 (m, J (F4,F3) ≈ J (F4,F5)
= 21.6 Hz, J (F4,F6) = 6.9 Hz, 1 F, F4). HRMS (EI): m/z [M]+ calcd for C9H5F4NO: 219.0302;
found: 219.0301.
4.2.1.13. 3-(2-Amino-3,4,5,6-tetrafluorophenyl)-1-phenylprop-2-yn-1-ol (8h)
Yellowish solid; yield: 248 mg (84%); Rf = 0.19 (EtOAc/hexane, 1:7, twice); mp 81.8–82.4 °C.
IR (KBr): 3412, 3298, 3217, 2241, 1660, 1604, 1518, 1498, 1458, 1304, 1269, 1201, 1161, 1125,
1
1041, 976, 870, 741, 698, 646, 578 cm–1. H NMR (300 MHz, CDCl3):  = 7.61–7.56 (m, 2 H,
13
Hm), 7.44–7.33 (m, 3 H, Ho + Hp), 5.74 (d, 1 H, OH), 4.25 (s, 2 H, H1), 2.44 (d, 1 H, H9). C
1
2
NMR (125.8 MHz, CDCl3):  = 147.9 (dm, J (C3,F3) = 248.7 Hz, J (C3,F4) = 11.0 Hz, C3),
141.6 (dm, J (C5,F5) = 252.9 Hz, J (C5,F4) ≈ J (C5,F6) = 14.0 Hz, C5), 139.8 (s, C10), 135.9
1
2
2
(dm, 1J (C6,F6) = 242.8 Hz, 2J (C6,F5) = 14.8 Hz, C6), 133.7 (dm, 2J (C1,F6) = 12 Hz, C1), 133.6
(dm, 1J (C4,F4) = 243.1 Hz, 2J (C4,F3) ≈ J (C4,F5) = 16.4 Hz, C4), 128.8 (s, C12), 128.7 (s, C13),
2
126.5 (s, C11), 100.6 (m, C7), 93.3 (dm, 2J (C2,F3) = 17.8 Hz, C2), 74.3 (m, C8), 65.1 (s, C9). 19F
NMR (282 MHz, CDCl3): δ = –138.6 (dm, J (F3,F4) = 22.2 Hz, J (F3,F6) = 9.7 Hz, J (F3,F5) = 3.4
Hz, 1 F, F3), –156.1 (m, J (F5,F4) ≈ J (F5,F6) = 20.9 Hz, J (F5,F3) = 3.4 Hz, 1 F, F5), –163.1 (m, J
(F6,F5) = 20.5 Hz, J (F6,F3) = 9.7 Hz, J (F6,F4) = 5.5 Hz, 1 F, F6), –173.8 (m, J (F4,F3) ≈ J (F4,F5)
= 21.6 Hz, J (F4,F6) = 5.5 Hz, 1 F, F4). HRMS (EI): m/z [M]+ calcd for C15H9F4NO: 295.0615;
found: 295.0613.
4.2.1.14. 3-(2-Amino-3,4,6-trifluoro-5-(trifluoromethyl)phenyl)-1-phenylprop-2-yn-1-ol (8i)
Yellowish oil; yield: 338 mg (98%); Rf = 0.28 (EtOAc/hexane, 1:5, twice). IR (thin): 3495, 3395,
3212, 2233, 1645, 1606, 1495, 1456, 1410, 1344, 1245, 1175, 1130, 1024, 986, 902, 753, 706,
639, 542 cm–1. 1H NMR (300 MHz, CDCl3):  = 7.56–7.54 (m, 2 H, Hm), 7.39–7.31 (m, 3 H, Ho
+ Hp), 5.69 (s, 1 H, H9), 5.07 (s, 2 H, H1), 4.76 (br. s, 1 H, OH). 13C NMR (125.8 MHz, CDCl3):
1
1
2
 = 156.2 (dm, J (C3,F3) = 256.4 Hz, C3), 147.9 (dm, J (C5,F5) = 258.9 Hz, J (C5,F6) = 13.3
Hz, C5), 141.7 (m, C1), 139.7 (s, C10), 135.1 (dm, J (C6,F6) = 238.4 Hz, J (C6,F5) = 15.0 Hz,
C6), 128.5 (s, C12), 128.4 (s, C13), 126.4 (s, C11), 121.7 (q, 1J (CF3,F) = 272.1 Hz, CF3), 100.6 (m,
C7), 96.0 (m, C4), 93.8 (dm, 2J (C2,F3) = 21.6 Hz, C2), 73.7 (m, C7), 64.6 (s, C9). 19F NMR (282
MHz, CDCl3): δ = –56.4 (t, J (CF3,F3) ≈ J (CF3,F5) = 21.4 Hz, 3 F, CF3), –114.7 (qd, J (F3,CF3)
= 21.6 Hz, J (F3,F6) = 11.1 Hz, 1 F, F3), –137.7 (m, J (F5,F6) ≈ J (F5,CF3) = 20.7 Hz, 1 F, F5), –
165.0 (dd, J (F6,F5) = 20.1 Hz, J (F6,F3) = 11.1 Hz, 1 F, F6). HRMS (EI): m/z [M]+ calcd for
C165H9F6NO: 345.0583; found: 345.0581.
1
2
4.2.2. 6-Ethynyl-2,3,4-trifluoroaniline (3g)
To a solution of 1 (300 mg, 1 mmol) and ethynyltrimethylsilane 2f (196 mg, 2 mmol) in
dry Et3N (10 mL) in a Schlenk flask under argon were added Pd(PPh3)2Cl2 (28 mg, 0.04 mmol)
and CuI (17 mg, 0.09 mmol). The reaction mixture was stirred at r.t. for 72 h. Then, the mixture
was diluted with CH2Cl2 (10 mL), poured into H2O (20 mL) and extracted with CH2Cl2 (3 × 50
mL). The combined organic layers were washed with H2O (20 mL) and dried (MgSO4). After
1
evaporation of the solvent in vacuo, the crude product (3f) was obtained (19F, H NMR spectra
are similar to those published earlier [20]). To a solution of 3f in MeOH (5 mL) K2CO3 (300 mg,
17

2 mmol) was added. The reaction mixture was stirred at r.t. for 2 h, then placed directly onto a
chromatography plate (silica gel), and air-dried. 2-Alkynylaniline 3g was isolated by TLC with
EtOAc/hexane (1:7) as an eluent, Rf = 0.65.
Yellowish oil; yield: 128 mg (75%); IR (thin): 3417, 3327, 3304, 3199, 2114, 1653, 1601, 1522,
1
1481, 1367, 1300, 1167, 1109, 1024, 908, 854, 715, 675, 617, 553, 445 cm–1. H NMR (300
MHz, CDCl3):  = 6.93 (ddd, J (H3,F4) = 11 Hz, J (H3,F5) = 8 Hz, J (H3,F6) = 2.3 Hz, 1 H, H3),
4.20 (s, 2 H, H1), 3.40 (s, 1 H, H8). 13C NMR (125.8 MHz, CDCl3):  = 142.7 (ddd, 1J (C4,F4) =
2
1
2
2
239.8 Hz, J (C4,F5) = 10.8 Hz, C4), 141.2 (ddd, J (C5,F5) = 252.6 Hz, J (C5,F6) = 16.5 Hz, J
(C5,F4) = 13.4 Hz, C5), 139.8 (ddd, J (C6,F6) = 242.3 Hz, 2J (C6,F5) = 12.5 Hz, C6), 135.2 (dm,
1
2J (C1,F6) = 11.1 Hz, C1), 114.4 (dd, 2J (C3,F4) = 19.4 Hz, 3J (C3,F5) = 3.6 Hz, C3), 101.7 (m, C2),
83.8 (m, C7), 77.6 (m, C8). 19F NMR (282 MHz, CDCl3): δ = –154.0 (ddd, J (F4,F5) = 21.4 Hz, J
(F4,H3) = 10.7 Hz, 1 F, F4), –157.8 (dt, J (F6,F5) = 19.2 Hz, J (F6,H3) = 2 Hz, 1 F, F6), –162.2 (m,
J (F5,F4) = 21.4 Hz, J (F5,F6) = 19.2 Hz, J (F5,H3) = 8.0 Hz, 1 F, F5). HRMS (EI): m/z [M]+ calcd
for C8H4F3N: 171.0290; found: 171.0289.
4.2.3. Interaction of 2-alkynylanilines 3 with PdCl2; General Procedure
To a solution of 3 (1 mmol) in MeCN (10 mL) PdCl2 (35 mg, 0.2 mmol) was added, and
the mixture was heated at reflux for 1 h with stirring. The mixture was allowed to cool to r.t.,
placed directly onto a chromatography plate (silica gel), and air-dried.
4.2.3.1. 5,6,7-Trifluoro-2-phenyl-1H-indole (4a)
Yellowish solid; yield: 237 mg (96%); Rf = 0.55 (EtOAc/hexane, 1:10); 19F, 1H NMR spectra are
similar to those published earlier [29].
4.2.3.2. 2-Butyl-5,6,7-trifluoro-1H-indole (4b)
Yellow oil; yield: 224 mg (99%); Rf = 0.75 (EtOAc/hexane, 1:10). IR (thin): 3475, 2960, 2933,
1
1862, 1601, 1524, 1477, 1414, 1377, 1325, 1198, 1061, 955, 845, 779, 727, 671, 449 cm–1. H
NMR (300 MHz, CDCl3):  = 8.29 (s, 1 H, H1), 7.00 (m, J (H4,F5) ≈ 9 Hz, J (H4,F6) ≈ 6.5 Hz, 1
H, H4), 6.16 (m, 1 H, H3), 2.72 (t, J (H8,H9) = 7.5 Hz, 2 H, H8), 1.73–1.63 (m, 2 H, H9), 1.45–
1.35 (m, 2 H, H10), 0.93 (t, J (H11,H10) = 7.5 Hz, 3 H, H11). 13C NMR (125.8 MHz, CDCl3):  =
146.7 (ddd, 1J (C5,F5) = 238.1 Hz, 2J (C5,F6) = 12.0 Hz, C5), 142.5 (m, C2), 137.5 (ddd, 1J (C7,F7)
= 246.5 Hz, 2J (C7,F6) = 13.4 Hz, 3J (C7,F5) = 4.6 Hz, C7), 135.7 (ddd, 1J (C6,F6) = 240.1 Hz, 2J
(C6,F5) = 18.4 Hz, 2J (C6,F7) = 12.3 Hz, C6), 124.4 (ddm, 2J (C7a,F7) = 9.7 Hz, C7a), 120.3 (dm, 3J
2
3
(C3a,F) = 9.5 Hz, C3a), 100.9 (dd, J (C4,F5) = 19.4 Hz, J (C4,F6) = 3.8 Hz, C4), 100.1 (m, C3),
31.1 (s, C8), 27.8 (s, C9), 22.3 (s, C10), 13.8 (s, C11). F NMR (282 MHz, CDCl3): δ = –147.3
19
(dd, J (F5,F6) = 20.4 Hz, J (F5,H4) = 10.2 Hz, 1 F, F5), –158.7 (dm, J (F7,F6) = 19.8 Hz, 1 F, F7),
–172.0 (td, J (F6,F5) ≈ J (F6,F7) = 20.1 Hz, J (F6,H4) = 6.5 Hz, 1 F, F6). HRMS (EI): m/z [M]+
calcd for C12H12F3N: 227.0916; found: 227.0917.
4.2.4. Interaction of 2-alkynylanilines 3 with KOH; General Procedure
To a solution of 3 (1 mmol) in MeCN (10 mL) KOH (112 mg, 2 mmol) was added, and
the mixture was heated at reflux for 4÷14 h (see Tables 4, 5) with stirring. Then, the mixture was
allowed to cool down to r.t., and H2O (10 mL) was added. The mixture was extracted with
18

CH2Cl2 (3 × 50 mL). The combined organic layers were washed with H2O (20 mL) and dried
(MgSO4). After evaporation of the solvent in vacuo, the crude product was purified by
preparative TLC.
4.2.4.1. 5,6,7-Trifluoro-1H-indole (4g)
Yellow oil; yield: 24 mg (14%); Rf = 0.65 (EtOAc/hexane, 1:10). IR (thin): 3483, 3305, 2962,
2927, 2854, 1714, 1651, 1601, 1516, 1473, 1373, 1336, 1321, 1261, 1194, 1055, 1018, 951, 881,
845, 800, 758, 719, 671, 571, 540, 457 cm–1. 1H NMR (300 MHz, CDCl3):  = 7.28 (d, 1 H, H1),
7.10 (m, J (H4,F5) = 9.7 Hz, J (H4,F6) = 6.5 Hz, 1 H, H4), 6.57 (s, 1 H, H2), 6.45 (m, 1 H, H3). 13C
1
2
NMR (125.8 MHz, CDCl3):  = 147.0 (dd, J (C5,F5) = 241.6 Hz, J (C5,F6) = 12.9 Hz, C5),
138.6 (ddd, J (C7,F7) ≈ 240 Hz, J (C7,F6) = 14.1 Hz, J (C7,F5) = 4.3 Hz, C7), 136.8 (ddd, J
(C6,F6) = 243.3 Hz, 2J (C6,F5) = 18.5 Hz, 2J (C6,F7) = 13.5 Hz, C6), 129.6 (dd, C2), 124.8 (m, 2J
(C7a,F7) = 9.4 Hz, C7a), 119.7 (dm, 3J (C3a,F) = 6.9 Hz, C3a), 104.8 (m, C3), 102.5 (dd, 2J (C4,F5)
= 19.1 Hz, J (C4,F6) = 3.7 Hz, C4). F NMR (282 MHz, CDCl3): δ = –144.8 (dd, J (F5,F6) =
20.5 Hz, J (F5,H4) = 9.7 Hz, 1 F, F5), –157.7 (dm, J (F7,F6) = 19.8 Hz, 1 F, F7), –168.5 (td, J
(F6,F5) ≈ J (F6,F7) = 20.1 Hz, J (F6,H4) = 6.5 Hz, 1 F, F6). HRMS (EI): m/z [M]+ calcd for
C8H4F3N: 171.0290; found: 171.0291.
1
2
3
1
3
19
4.2.5. Interaction of 2-alkynylanilines with p-TSAH2O; General Procedure
To a solution of 3, 8a-e (1 mmol) in EtOH, MeOH or benzene (15 mL) p-TSA
monohydrate (380 mg, 2 mmol) was added, and the mixture was heated at reflux for 1÷15 h (see
Tables 6 – 11) with stirring. The mixture was allowed to cool to r.t., placed directly onto a
chromatography plate (silica gel), and air-dried. Reaction products were isolated by TLC with
EtOAc/hexane as an eluent.
4.2.5.1. 2-(Ethoxymethyl)-5,6,7-trifluoro-1H-indole (4h)
Yellow solid; yield: 85 mg (37%); Rf = 0.25 (CH2Cl2/hexane, 1:1); mp 121.3–123.6 °C. IR
(KBr): 3439, 2927, 2856, 1632, 1525, 1477, 1429, 1385, 1200, 1105, 953, 876, 843, 791, 671,
567, 472 cm–1. 1H NMR (300 MHz, CDCl3):  = 8.58 (s, 1 H, H1), 7.06 (m, J (H4,F5) ≈ J (H4,F6)
≈ 8 Hz, 1 H, H4), 6.35 (m, 1 H, H3), 4.61 (s, 2 H, H8), 3.56 (q, J (H9,H10) = 6.9 Hz, 2 H, H9), 1.24
13
1
(t, J (H10,H9) = 6.9 Hz,3 H, H10). C NMR (125.8 MHz, CDCl3):  = 146.7 (ddd, J (C5,F5) =
239.0 Hz, 2J (C5,F6) = 13.4 Hz, C5), 137.7 (m, C2), 137.6 (ddd, 1J (C7,F7) = 247.7 Hz, 2J (C7,F6)
= 13.5 Hz, J (C7,F5) = 4.6 Hz, C7), 136.1 (ddd, J (C6,F6) = 241.9 Hz, J (C6,F5) = 18.5 Hz, J
3
1
2
2
(C6,F7) = 12.3 Hz, C6), 123.4 (ddm, J (C7a,F7) = 9.8 Hz, C7a), 120.9 (dm, J (C3a,F) = 10.2 Hz,
C3a), 101.7 (m, C3), 101.4 (dd, 2J (C4,F5) = 19.4 Hz, 3J (C4,F6) = 3.9 Hz, C4), 65.9 (s, C8), 69.2 (s,
C9), 14.9 (s, C10). 19F NMR (282 MHz, CDCl3): δ = –146.5 (dd, J (F5,F6) = 20.3 Hz, J (F5,H4) =
10.1 Hz, 1 F, F5), –158.1 (dm, J (F7,F6) = 19.6 Hz, 1 F, F7), –172.3 (td, J (F6,F5) ≈ J (F6,F7) =
20.0 Hz, J (F6,H4) = 6.5 Hz, 1 F, F6). HRMS (EI): m/z [M]+ calcd for C11H10F3NO: 229.0709;
found: 229.0707.
2
3
4.2.5.2. 5,6,7-Trifluoro-2-(methoxymethyl)-1H-indole (4i)
Yellowish solid; yield: 39 mg (18%); Rf = 0.25 (CH2Cl2/hexane, 1:1); mp 122.5–123.4 °C. IR
(KBr): 3240, 2956, 2929, 2837, 1601, 1568, 1525, 1475, 1381, 1350, 1317, 1200, 1163, 1080,
19

1
1061, 1001, 978, 949, 897, 845, 795, 727, 669, 627, 575, 546, 496 cm–1. H NMR (300 MHz,
CDCl3):  = 8.59 (s, 1 H, H1), 7.07 (m, J (H4,F5) = 10.1 Hz, J (H4,F6) = 6.7 Hz, J (H4,H3) = 2
13
Hz,1 H, H4), 6.36 (m, J (H3,H4) = 2 Hz,1 H, H3), 4.57 (s, 2 H, H8), 3.39 (s, 3 H, H9). C NMR
(125.8 MHz, CDCl3):  = 146.6 (ddd, 1J (C5,F5) = 239.1 Hz, 2J (C5,F6) = 12 Hz, C5), 138.4 (ddd,
1J (C7,F7) = 247.6 Hz, 2J (C7,F6) = 13.5 Hz, 3J (C7,F5) = 4.5 Hz, C7), 137.2 (m, C2), 136.3 (ddd,
1J (C6,F6) = 242.1 Hz, 2J (C6,F5) = 18.6 Hz, 2J (C6,F7) = 12.3 Hz, C6), 123.4 (ddm, 2J (C7a,F7) =
10 Hz, C7a), 121.0 (dm, 3J (C3a,F) = 10 Hz, C3a), 102.1 (m, C3), 101.5 (dd, 2J (C4,F5) = 19.4 Hz,
3J (C4,F6) = 3.9 Hz, C4), 67.1 (s, C8), 57.9 (s, C9). 19F NMR (282 MHz, CDCl3): δ = –143.6 (dd,
J (F5,F6) = 20.3 Hz, J (F5,H4) = 10.1 Hz, 1 F, F5), –155.3 (dm, J (F7,F6) = 19.7 Hz, 1 F, F7), –
164.3 (td, J (F6,F5) ≈ J (F6,F7) = 19.9 Hz, J (F6,H4) = 6.5 Hz, 1 F, F6). HRMS (EI): m/z [M]+
calcd for C10H8F3NO: 215.0553; found: 215.0550.
4.2.5.3. 5,6,7-Trifluoro-2-(prop-1-en-2-yl)-1H-indole (4j)
White solid; yield: 29 mg (14%); Rf = 0.65 (EtOAc/hexane, 1:5, twice); mp 66.9 °C (dec.). IR
(KBr): 3479, 3070, 2926, 2854, 1792, 1713, 1630, 1599, 1520, 1477, 1379, 1315, 1269, 1230,
1186, 1142, 1101, 1059, 958, 891, 864, 798, 719, 675, 553, 501, 436 cm–1. 1H NMR (300 MHz,
CDCl3):  = 8.25 (s, 1 H, H1), 7.07 (m, J (H4,F5) = 9.9 Hz, J (H4,F6) = 6.5 Hz, 1 H, H4), 6.47 (m,
1 H, H3), 5.34 (s, 1 H, H9’), 5.13 (m, 1 H, H9), 2.15 (m, 3 H, H10). 13C NMR (125.8 MHz,
CDCl3):  = 146.9 (dd, J (C5,F5) = 239.1 Hz, J (C5,F6) = 11.8 Hz, C5), 140.7 (m, C2), 137.4
(ddd, 1J (C7,F7) = 247.3 Hz, 2J (C7,F6) = 14.0 Hz, 3J (C7,F5) = 4.6 Hz, C7), 136.8 (ddd, 1J (C6,F6)
= 243.6 Hz, 2J (C6,F5) = 18.8 Hz, 2J (C6,F7) = 12.6 Hz, C6), 134.3 (s, C8), 124.2 (ddm, 2J (C7a,F7)
1
2
3
2
= 10.5 Hz, C7a), 121.2 (dm, J (C3a,F) = 10 Hz, C3a), 110.9 (s, C9), 101.8 (dd, J (C4,F5) = 19.6
Hz, J (C4,F6) = 3.9 Hz, C4), 101.5 (m, C3), 20.3 (s, C10). F NMR (282 MHz, CDCl3): δ = –
146.3 (dd, J (F5,F6) = 20.2 Hz, J (F5,H4) = 10.0 Hz, 1 F, F5), –158.3 (dm, J (F7,F6) = 19.5 Hz, 1
F, F7), –169.2 (td, J (F6,F5) ≈ J (F6,F7) = 19.9 Hz, J (F6,H4) = 6.6 Hz, 1 F, F6). HRMS (EI): m/z
[M]+ calcd for C11H8F3N: 211.0603; found: 211.0609.
3
19
4.2.5.4. 1-(2-Amino-3,4,5-trifluorophenyl)-3-ethoxypropan-1-one (5h)
Yellowish solid; yield: 57 mg (23%); Rf = 0.30 (CH2Cl2/hexane, 1:1); mp 51.5–64.6 °C. IR
(KBr): 3458, 3340, 2982, 2943, 2893, 1657, 1597, 1560, 1525, 1456, 1389, 1325, 1300, 1275,
1
1223, 1155, 1101, 1066, 1026, 978, 877, 852, 696, 600, 496, 444 cm–1. H NMR (300 MHz,
CDCl3):  = 7.35 (ddd, J (H3,F4) = 10.7 Hz, J (H3,F5) = 8.0 Hz, J (H3,F6) = 2.2 Hz, 1 H, H3), 6.28
(s, 2 H, H1), 3.76 (t, J (H9,H8) = 6.4 Hz, 2 H, H9), 3.48 (q, J (H10,H11) = 7.0 Hz, 2 H, H10), 3.07
(t, J (H8,H9) = 6.4 Hz, 2 H, H8), 1.14 (t, J (H11,H10) = 7.0 Hz, 3 H, H11). 13C NMR (125.8 MHz,
CDCl3):  = 198.8 (m, C7), 143.4 (dm, 1J (C4,F4) = 240.5 Hz, C4), 141.1 (dm, 1J (C5,F5) = 245.4
1
2
2
Hz, C5), 139.8 (ddd, J (C6,F6) = 243.8 Hz, J (C6,F5) = 11.5 Hz, C6), 137.8 (dm, J (C1,F6) =
10.4 Hz, C1), 112.7 (m, C2), 112.4 (dm, J (C3,F4) = 17.7 Hz, J (C3,F5) = 3.7 Hz, C3), 66.5 (s,
C9), 65.5 (s, C10), 39.4 (s, C8), 15.0 (s, C11). F NMR (282 MHz, CDCl3): δ = –149.4 (ddd, J
2
3
19
(F4,F5) = 22.0 Hz, J (F4,H3) = 11.2 Hz, 1 F, F4), –149.8 (m, J (F5,F4) = 22.0 Hz, J (F5,F6) = 18.5
Hz, J (F5,H3) = 8.0 Hz, 1 F, F5), –155.6 (dt, J (F6,F5) = 18.5 Hz, J (F6,H3) = 2.2 Hz, 1 F, F6).
HRMS (EI): m/z [M]+ calcd for C11H12F3NO2: 247.0815; found: 247.0819.
4.2.5.5. 1-(2-Amino-3,4,5-trifluorophenyl)-3-methoxypropan-1-one (5i)
20

Yellowish solid; yield: 77 mg (33%); Rf = 0.34 (CH2Cl2/hexane, 1:1); mp 61.0–61.3 °C. IR
(KBr): 3442, 3327, 2983, 2929, 2818, 1662, 1599, 1574, 1525, 1464, 1423, 1394, 1333, 1300,
1
1275, 1203, 1153, 1119, 1072, 1028, 964, 862, 810, 696, 575, 501, 447 cm–1. H NMR (300
MHz, CDCl3):  = 7.38 (ddd, J (H3,F4) = 10.7 Hz, J (H3,F5) = 8.0 Hz, J (H3,F6) = 2.2 Hz, 1 H,
H3), 6.33 (s, 2 H, H1), 3.78 (t, J (H9,H8) = 6.2 Hz, 2 H, H9), 3.38 (s, Hz, 3 H, H10), 3.11 (t, J
13
1
(H8,H9) = 6.2 Hz, 2 H, H8). C NMR (125.8 MHz, CDCl3):  = 198.6 (m, C7), 143.3 (dm, J
(C4,F4) = 240.4 Hz, C4), 139.9 (dm, J (C5,F5) = 243.5 Hz, C5), 139.5 (ddd, J (C6,F6) = 243.7
Hz, 2J (C6,F5) = 11.5 Hz, C6), 137.9 (dm, 2J (C1,F6) = 10.3 Hz, C1), 112.5 (m, C2), 112.3 (dm, 2J
(C3,F4) = 17.7 Hz, 3J (C3,F5) = 3.6 Hz, C3), 67.5 (s, C9), 58.8 (s, C10), 39.1 (s, C8). 19F NMR (282
MHz, CDCl3): δ = –149.4 (ddd, J (F4,F5) = 22.0 Hz, J (F4,H3) = 11.2 Hz, 1 F, F4), –149.7 (m, J
(F5,F4) = 22.0 Hz, J (F5,F6) = 18.5 Hz, J (F5,H3) = 8.0 Hz, 1 F, F5), –155.5 (dm, J (F6,F5) = 18.5
Hz, 1 F, F6). HRMS (EI): m/z [M]+ calcd for C10H10F3NO2: 233.0658; found: 233.0661.
1
1
4.2.5.6. 6,7,8-Trifluoro-2,3-dihydroquinolin-4(1H)-one (6c)
Yellowish solid; yield: 80 mg (40%); Rf = 0.50 (EtOAc/hexane, 1:3, twice); mp 174.9–176.3 °C.
IR (KBr): 3325, 3070, 2991, 2875, 1668, 1651, 1597, 1539, 1504, 1398, 1342, 1281, 1197, 1163,
1
1109, 1059, 1041, 997, 883, 845, 658, 627, 579, 523, 472, 417 cm–1. H NMR (300 MHz,
CDCl3): δ = 7.45 (m, J (H5,F6) = 10.2 Hz, J (H5,F7) = 8.1 Hz, 1 H, H5), 4.57 (s, 1 H, H1), 3.63 (t,
J (H2,H3) = 7 Hz, 2 H, H2), 2.72 (t, J (H3,H2) = 7 Hz, 2 H, H3). 13C NMR (125 MHz, CDCl3): δ =
190.4 (m, C4), 144.1 (ddd, 1J (C7,F7) = 258.3 Hz, 2J (C7,F6) = 17.7 Hz, 2J (C7,F8) = 12.7 Hz, C7),
143.7 (ddd, 1J (C6,F6) = 243.0 Hz, 2J (C6,F7) = 11.2 Hz, C6), 139.6 (ddd, 1J (C8,F8) = 245.9 Hz, 2J
2
2
(C8,F7) = 12.4 Hz, C8), 138.8 (dm, J (C8a,F8) = 10 Hz, C8a), 114.2 (m, C4a), 109.1 (ddm, J
(C5,F6) = 18.1 Hz, J (C5,F7) = 3.8 Hz, C5), 42.2 (s, C2), 37.7 (s, C3). 19F NMR (282 MHz,
3
CDCl3): δ = –149.7 (ddd, J (F6,F7) = 21.7 Hz, J (F6,H5) = 10.2 Hz, 1 F, F6), –151.8 (m, J (F7,F6)
= 21.7 Hz, J (F7,F8) = 18.5 Hz, J (F7,H5) = 8.1 Hz, 1 F, F7), –157.4 (dm, J (F8,F7) = 18.5 Hz, 1 F,
F8). HRMS (EI): m/z [M-H]+ calcd for C9H5F3NO: 200.0318; found: 200.0319.
4.2.5.7. 6,7,8-Trifluoro-2-isopropyl-2,3-dihydroquinolin-4(1H)-one (6d)
Yellowish solid; yield: 197 mg (81%); Rf = 0.45 (EtOAc/hexane, 1:10); mp 99.4–99.5 °C. IR
(KBr): 3346, 3095, 2964, 2935, 2877, 1668, 1653, 1527, 1508, 1462, 1387, 1259, 1275, 1178,
1082, 1059, 1007, 916, 883, 852, 704, 621, 602, 501, 455 cm–1. 1H NMR (300 MHz, CDCl3): δ =
7.40 (m, J (H5,F6) = 10.2 Hz, J (H5,F7) = 8.1 Hz, 1 H, H5), 4.45 (s, 1 H, H1), 3.44 (m, 1 H, H2),
2.67–2.47 (m, 2 H, H3), 1.90 (m, 1 H, H9), 1.02 (s, 3 H, H10), 1.00 (s, 3 H, H10’). 13C NMR (125
1
2
2
MHz, CDCl3): δ = 192.8 (m, C4), 145.6 (ddd, J (C7,F7) = 258.1 Hz, J (C7,F6) = 17.7 Hz, J
(C7,F8) = 12.8 Hz, C7), 145.0 (ddd, 1J (C6,F6) = 242.9 Hz, 2J (C6,F7) = 11.2 Hz, C6), 141.1 (ddd,
1J (C8,F8) = 245.6 Hz, 2J (C8,F7) = 12.4 Hz, C8), 140.0 (dm, 2J (C8a,F8) = 10 Hz, C8a), 115.3 (m,
C4a), 110.2 (ddm, 2J (C5,F6) = 18.0 Hz, 3J (C5,F7) = 3.8 Hz, C5), 60.4 (s, C2), 41.7 (s, C3), 33.0 (s,
C9), 19.6 (s, C10), 19.2 (s, C10’). 19F NMR (282 MHz, CDCl3): δ = –149.9 (ddd, J (F6,F7) = 21.7
Hz, J (F6,H5) = 10.2 Hz, 1 F, F6), –152.0 (m, J (F7,F6) = 21.7 Hz, J (F7,F8) = 18.5 Hz, J (F7,H5) =
8.1 Hz, 1 F, F7), –157.5 (dm, J (F8,F7) = 18.5 Hz, 1 F, F8). HRMS (EI): m/z [M]+ calcd for
C12H12F3NO: 243.0866; found: 243.0867.
4.2.5.8. 6,7,8-Trifluoro-2,2-dimethyl-2,3-dihydroquinolin-4(1H)-one (6e)
21

Yellowish solid; yield: 172 mg (75%); Rf = 0.53 (EtOAc/hexane, 1:7, twice); mp 118.8–120.2
°C. IR (KBr): 3334, 3005, 3078, 2976, 2889, 1670, 1649, 1533, 1500, 1471, 1311, 1282, 1207,
1165, 1115, 1078, 1026, 922, 883, 862, 771, 658, 619, 590, 528, 442 cm–1. 1H NMR (500 MHz,
CDCl3): δ = 7.40 (m, J (H5,F6) = 10.0 Hz, J (H5,F7) = 8.0 Hz, 1 H, H5), 4.32 (s, 1 H, H1), 2.59 (s,
1
2 H, H3), 1.33 (s, 6 H, H9). 13C NMR (125 MHz, CDCl3): δ = 191.0 (m, C4), 144.3 (ddd, J
(C7,F7) = 257.8 Hz, 2J (C7,F6) = 17.6 Hz, 2J (C7,F8) = 12.9 Hz, C7), 143.1 (ddd, 1J (C6,F6) = 242.3
Hz, 2J (C6,F7) = 11.1 Hz, C6), 139.4 (ddd, 1J (C8,F8) = 245.3 Hz, 2J (C8,F7) = 12.5 Hz, C8), 136.8
(dm, 2J (C8a,F8) = 10 Hz, C8a), 112.7 (m, C4a), 108.6 (ddm, 2J (C5,F6) = 18.0 Hz, 3J (C5,F7) = 3.7
Hz, C5), 54.1 (s, C2), 50.2 (s, C3), 27.4 (s, C9). 19F NMR (282 MHz, CDCl3): δ = –150.6 (ddm, J
(F6,F7) = 21.7 Hz, J (F6,H5) = 10.0 Hz, 1 F, F6), –151.9 (m, J (F7,F6) = 21.7 Hz, J (F7,F8) = 18.5
Hz, J (F7,H5) = 8.0 Hz, 1 F, F7), –157.7 (dm, J (F8,F7) = 18.5 Hz, 1 F, F8). HRMS (EI): m/z [M]+
calcd for C11H10F3NO: 229.0709; found: 229.0712.
4.2.5.9. 2,3-Dihydroquinolin-4(1H)-one (9a)
Yellow oil; yield: 15 mg (10%); Rf = 0.60 (EtOAc/hexane, 1:2, 5 times). IR (thin): 3392, 2958,
2925, 2854, 1660, 1612, 1512, 1439, 1359, 1240, 1153, 1122, 1095, 1055, 895, 762, 559, 445
cm–1. 1H NMR (400 MHz, Acetone-d6): δ = 7.68 (dm, J (H5,H6) = 7.9 Hz, 1 H, H5), 7.25 (tm, J
(H7,H8) = 8.4 Hz, J (H7,H6) = 7.0 Hz, 1 H, H7), 6.78 (dm, J (H8,H7) = 8.4 Hz, 1 H, H8), 6.62 (tm,
J (H6,H5) = 7.9 Hz, J (H6,H7) = 7.0 Hz, 1 H, H6), 5.97 (s, 1 H, H1), 3.52 (m, 2 H, H2), 2.55 (t, J
13
(H3,H2) = 7.6 Hz, 2 H, H3). 1H NMR spectrum is close to that published earlier [32]. C NMR
(125 MHz, Acetone-d6): δ = 193.3 (s, C4), 153.8 (s, C8a), 135.4 (s, C7), 127.7 (s, C5), 119.6 (s,
C4a), 117.4 (s, C6), 116.8 (s, C8), 42.4 (s, C2), 38.6 (s, C3). HRMS (EI): m/z [M-H]+ calcd for
C9H9NO: 147.0679; found: 147.0679.
4.2.5.10. 2-Phenyl-2,3-dihydroquinolin-4(1H)-one (9b)
Yellowish solid; yield: 149 mg (67%); Rf = 0.33 (EtOAc/hexane, 1:5, 4 times); mp 148.9 °C
(decomp.) (149–150 °C [34]). IR (KBr): 3332, 1657, 1604, 1508, 1495, 1481, 1333, 1304, 1261,
1
1215, 1153, 1115, 1026, 997, 916, 766, 700, 650, 565, 492, 442 cm–1. H NMR (500 MHz,
Acetone-d6): δ = 7.71 (dm, J (H5,H6) = 8.0 Hz, 1 H, H5), 7.55 – 7.51 (m, 2 H, Hm), 7.39 – 7.20
(m, 4 H, 2 Ho + H7 + Hp), 6.96 (dm, J (H8,H7) = 8.3 Hz, 1 H, H8), 6.70 (tm, J (H6,H5) = 8.0 Hz, J
(H6,H7) = 7.0 Hz, 1 H, H6), 6.21 (s, 1 H, H1), 4.79 (dd, J (H2,H3) = 12.9 Hz, J (H2,H3’) = 4.0 Hz,
1 H, H2), 2.82 (dd, J (H3,H3’) = 16.1 Hz, J (H3,H2) = 12.9 Hz, 1 H, H3), 2.67 (dm, J (H3’,H2) =
16.1 Hz, J (H3’,H2) = 4.0 Hz, 1 H, H3’). 1H NMR spectrum is close to that published earlier [33].
13C NMR (125 MHz, Acetone-d6): δ = 192.9 (s, C4), 153.3 (s, C8a), 142.1 (s, C9), 135.7 (s, C7),
129.4 (s, C11), 128.7 (s, C12), 127.6 (s, C10), 127.5 (s, C5), 119.4 (s, C4a), 118.0 (s, C6), 117.1 (s,
C8), 58.4 (s, C2), 46.8 (s, C3). HRMS (EI): m/z [M]+ calcd for C15H13NO: 223.0992; found:
223.0993.
4.2.5.11. 6,8-Difluoro-2,3-dihydroquinolin-4(1H)-one (9c)
Yellowish solid; yield: 16 mg (9%); Rf = 0.22 (EtOAc/hexane, 1:5, 3 times). IR (KBr): 3349,
2927, 2856, 1676, 1660, 1539, 1510, 1423, 1346, 1279, 1184, 1157, 1101, 1059, 1018, 893, 848,
667, 592, 550 cm–1. 1H NMR (300 MHz, Acetone-d6): δ = 7.23 – 7.13 (m, 2 H, H5 + H7), 5.93 (s,
1 H, H1), 3.62 (m, 2 H, H2), 2.65 (t, J (H3,H2) = 6.5 Hz, 2 H, H3). 13C NMR (125 MHz, Acetone-
1
3
1
d6): δ = 191.9 (t, C4), 153.8 (dd, J (C6,F6) = 236.9 Hz, J (C6,F8) = 10.5 Hz, C6), 151.9 (dd, J
22

3
2
(C8,F8) = 245.3 Hz, J (C8,F6) = 11.1 Hz, C8), 139.7 (dd, J (C8a,F8) = 13.5 Hz, C8a), 120.7 (dd,
C4a), 109.5 (dd, 2J (C7,F6) = 28.7 Hz, 2J (C7,F8) = 22.0 Hz, C7), 107.6 (dd, 2J (C5,F6) = 22.0 Hz,
C5), 42.4 (s, C2), 38.4 (s, C3). F NMR (282 MHz, Acetone-d6): δ = –125.8 (t, J (F6,H5) ≈ J
19
(F6,H7) = 11 Hz, 1 F, F6), –130.4 (d, J (F8,F6) = 11 Hz, 1 F, F8). HRMS (EI): m/z [M]+ calcd for
C9H7F2NO: 183.0490; found: 183.0485.
4.2.5.12. 6,7,8-Trifluoro-2-phenyl-2,3-dihydroquinolin-4(1H)-one (9d)
Yellowish solid; yield: 249 mg (90%); Rf = 0.39 (EtOAc/hexane, 1:7, twice); mp 155.6 °C
(decomp.). IR (KBr): 3315, 3062, 3035, 2974, 2872, 1668, 1647, 1601, 1527, 1502, 1456, 1383,
1365, 1277, 1209, 1157, 1063, 1020, 997, 920, 870, 854, 760, 706, 663, 621, 598, 530, 509, 478,
436 cm–1. 1H NMR (500 MHz, CDCl3): δ = 7.49 – 7.36 (m, 6 H, H5 + 2 Hm + 2 Ho + Hp), 4.76 –
13
4.73 (m, 2 H, H2 + H1), 2.91 – 2.77 (m, 2 H, H3). C NMR (125 MHz, CDCl3): δ = 190.3 (m,
1
2
2
C4), 144.3 (ddd, J (C7,F7) = 258.8 Hz, J (C7,F6) = 17.7 Hz, J (C7,F8) = 12.8 Hz, C7), 143.8
(ddd, J (C6,F6) = 243.6 Hz, J (C6,F7) = 12.5 Hz, C6), 139.7 (s, C9), 139.6 (ddd, J (C8,F8) =
246.3 Hz, 2J (C8,F7) = 12.5 Hz, C8), 138.4 (dm, 2J (C8a,F8) = 10.4 Hz, C8a), 129.0 (s, C11), 128.8
(s, C12), 126.4 (s, C10), 113.8 (m, C4a), 109.0 (dm, 2J (C5,F6) = 18.2 Hz, C5), 58.4 (s, C2), 46.0 (s,
C3). 19F NMR (282 MHz, CDCl3): δ = –148.8 (dd, J (F6,F7) = 21.7 Hz, J (F6,H5) = 10.1 Hz, 1 F,
F6), –151.2 (m, J (F7,F6) = 21 Hz, J (F7,F8) = 19 Hz, J (F7,H5) = 8 Hz, 1 F, F7), –156.6 (dm, J
(F8,F7) = 19 Hz, 1 F, F8). HRMS (EI): m/z [M-H]+ calcd for C15H10F3NO: 277.0709; found:
277.0705.
1
2
1
4.2.5.13. 5,6,8-Ttrifluoro-2,3-dihydroquinolin-4(1H)-one (9e)
Yellowish solid; yield: 28 mg (14%); Rf = 0.40 (EtOAc/hexane, 1:7, 3 times); mp 131.2 °C
(decomp.). IR (KBr): 3338, 3080, 2983, 1666, 1527, 1454, 1394, 1346, 1306, 1261, 1188, 1138,
1076, 1051, 999, 864, 839, 714, 575, 496 cm–1. 1H NMR (300 MHz, Acetone-d6): δ = 7.36 (td, J
(H7,H8) ≈ J (H7,H6) = 10.6 Hz, J (H7,F5) = 6.9 Hz, 1 H, H7), 6.14 (s, 1 H, H1), 3.63 (m, 2 H, H2),
2.64 (t, 2 H, J (H3,H2) = 6.9 Hz, H3). 13C NMR (125 MHz, Acetone-d6): δ = 190.3 (t, C4), 146.5
1
2
1
3
(ddd, J (C5,F5) = 257.8 Hz, J (C5,F6) = 12.8 Hz, C5), 146.3 (ddd, J (C8,F8) = 240.7 Hz, J
(C8,F6) = 9.5 Hz, C8), 140.5 (ddd, 1J (C6,F6) = 236.7 Hz, 2J (C6,F5) = 14.0 Hz, C6), 139.5 (dt, 2J
(C8a,F8) = 14.1 Hz, C8a), 110.1 (td, J (C7,F6) ≈ J (C7,F8) = 23.6 Hz, C7), 108.0 (dm, C4a), 41.8
(s, C2), 39.3 (s, C3). 19F NMR (282 MHz, Acetone-d6): δ = –136.4 (m, J (F8,F5) = 17 Hz, J
(F8,H7) = 10.9 Hz, J (F8,F6) = 2.7 Hz, 1 F, F8), –145.8 (m, J (F5,F6) = 20 Hz, J (F5,F8) = 17.1 Hz,
J (F5,H7) = 6.9 Hz, 1 F, F5), –153.6 (ddd, J (F6,F5) = 19.7 Hz, J (F6,H7) = 10.4 Hz, J (F6,F8) = 3
Hz, 1 F, F6). HRMS (EI): m/z [M-H]+ calcd for C9H5F3NO: 200.0318; found: 200.0317.
2
2
4.2.5.14. 5,6,8-Trifluoro-2-phenyl-2,3-dihydroquinolin-4(1H)-one (9f)
Yellowish solid; yield: 235 mg (85%); Rf = 0.53 (EtOAc/hexane, 1:7, 3 times); mp 160.5 °C
(decomp.). IR (KBr): 3396, 3055, 1678, 1645, 1601, 1516, 1387, 1331, 1298, 1259, 1192, 1142,
1018, 982, 897, 847, 786, 731, 698, 586, 488 cm–1. 1H NMR (500 MHz, CDCl3): δ = 7.43 – 7.33
(m, 5 H, 2 Hm + 2 Ho + Hp), 7.07 (m, J (H7,H8) ≈ J (H7,H6) = 10.1 Hz, J (H7,F5) = 6.7 Hz, 1 H,
H7), 4.75 – 4.72 (m, 2 H, H2 + H1), 2.94 – 2.76 (m, 2 H, H3). 13C NMR (125 MHz, CDCl3): δ =
189.6 (s, C4), 145.8 (dm, 1J (C5,F5) = 257.5 Hz, 2J (C5,F6) = 13.0 Hz, C5), 145.2 (dm, 1J (C8,F8) =
3
1
2
241.6 Hz, J (C8,F6) = 9.1 Hz, C8), 140.8 (dm, J (C6,F6) = 241.9 Hz, J (C6,F5) = 14.1 Hz, C6),
139.6 (s, C9), 136.9 (dm, 2J (C8a,F8) = 14.0 Hz, C8a), 129.0 (s, C11), 128.7 (s, C12), 126.4 (s, C10),
23

2
2
19
109.9 (tm, J (C7,F6) ≈ J (C7,F8) = 24.6 Hz, C7), 109.8 (m, C4a), 57.7 (s, C2), 47.0 (s, C3). F
NMR (282 MHz, CDCl3): δ = –138.1 (m, J (F8,F5) = 17.0 Hz, J (F8,H7) = 10.3 Hz, J (F8,F6) = 2.7
Hz, 1 F, F8), –145.8 (m, J (F5,F6) = 20.2 Hz, J (F5,F8) = 17.0 Hz, J (F5,H7) = 6.7 Hz, 1 F, F5), –
151.3 (ddd, J (F6,F5) = 20.2 Hz, J (F6,H7) = 9.6 Hz, J (F6,F8) = 2.7 Hz, 1 F, F6). HRMS (EI): m/z
[M-H]+ calcd for C15H10F3NO: 277.0709; found: 277.0712.
4.2.5.15. 5,6,7,8-Tetrafluoro-2,3-dihydroquinolin-4(1H)-one (9g)
White solid; yield: 32 mg (15%); Rf = 0.57 (EtOAc/hexane, 1:2, 3 times); mp 162.5 °C
(decomp.). IR (KBr): 3359, 2927, 2856, 1676, 1660, 1539, 1510, 1423, 1346, 1279, 1184, 1157,
1101, 1059, 1018, 893, 848, 667, 592, 561 cm–1. 1H NMR (300 MHz, Acetone-d6): δ = 6.47 (s, 1
13
H, H1), 3.66 (m, 2 H, H2), 2.65 (t, J (H3,H2) = 6.7 Hz, 2 H, H3). C NMR (125 MHz, Acetone-
d6): δ = 189.4 (s, C4), 147.9 (dm, 1J (C5,F5) = 259.6 Hz, 2J (C5,F6) = 10.2 Hz, C5), 144.6 (dm, 1J
2
2
1
(C7,F7) = 252.9 Hz, J (C7,F6) ≈ J (C7,F8) = 13.5 Hz, C7), 138.4 (dm, J (C8,F8) = 250 Hz, C8),
135.5 (m, C8a), 132.4 (dm, 1J (C6,F6) = 238.5 Hz, 2J (C6,F5) ≈ 2J (C6,F7) = 16 Hz, C6), 105.4 (m,
C4a), 41.7 (s, C2), 39.1 (s, C3). 19F NMR (282 MHz, Acetone-d6): δ = –143.1 (m, J (F5,F6) = 20.6
Hz, J (F5,F8) = 12.4 Hz, J (F5,F7) = 8.2 Hz, 1 F, F5), –151.5 (m, J (F7,F6) = 20.6 Hz, J (F7,F8) =
19.5 Hz, J (F7,F5) = 8.2 Hz, 1 F, F7), –163.0 (m, J (F8,F7) = 19.5 Hz, J (F8,F5) = 12.4 Hz, J
(F8,F6) = 7.1 Hz, 1 F, F8), –177.2 (m, J (F6,F7) ≈ J (F6,F5) = 20.4 Hz, J (F6,F8) = 7.1 Hz, 1 F, F6).
HRMS (EI): m/z [M]+ calcd for C9H5F4NO: 219.0302; found: 219.0304.
4.2.5.16. 5,6,7,8-Tetrafluoro-2-phenyl-2,3-dihydroquinolin-4(1H)-one (9h)
White solid; yield: 262 mg (89%); Rf = 0.44 (EtOAc/hexane, 1:7, twice); mp 188.9–189.3 °C. IR
(KBr): 3315, 3035, 2974, 2885, 1674, 1656, 1508, 1458, 1365, 1333, 1311, 1271, 1211, 1173,
1
1145, 1080, 1036, 989, 924, 862, 764, 702, 642, 559, 478 cm–1. H NMR (300 MHz, Acetone-
d6): δ = 7.50 – 7.46 (m, 2 H, Hm), 7.41 – 7.30 (m, 3 H, 2 Ho + Hp), 6.65 (s, 1 H, H1), 4.96 (dm, J
(H2,H3) = 11.0 Hz, J (H2,H3’) = 4.6 Hz,1 H, H2), 2.97 (dd, J (H3,H3’) = 15.8 Hz, J (H3,H2) = 11.0
Hz, 1 H, H3), 2.85 – 2.78 (m, J (H3’,H3) = 15.8 Hz, J (H3’,H2) = 4.6 Hz, 1 H, H3’). 13C NMR (125
MHz, Acetone-d6): δ = 189.4 (s, C4), 148.2 (dm, 1J (C5,F5) = 260.0 Hz, 2J (C5,F6) = 10.0 Hz, C5),
145.5 (dm, 1J (C7,F7) = 253.8 Hz, 2J (C7,F6) ≈ 2J (C7,F8) = 13.8 Hz, C7), 141.9 (s, C9), 139.4 (m,
1
2
1
C8a), 137.1 (dm, J (C8,F8) = 242.4 Hz, J (C8,F7) = 12.1 Hz, C8), 133.4 (dm, J (C6,F6) = 240.4
Hz, 2J (C6,F5) ≈ 2J (C6,F7) = 15.3 Hz, C6), 130.1 (s, C11), 129.5 (s, C12), 128.0 (s, C10), 106.1 (dm,
2J (C4a,F5) = 8 Hz, C4a), 57.9 (s, C2), 47.5 (s, C3). 19F NMR (282 MHz, Acetone-d6): δ = –143.3
(m, J (F5,F6) = 20.4 Hz, J (F5,F8) = 12.4 Hz, J (F5,F7) = 8.3 Hz, 1 F, F5), –150.8 (m, J (F7,F6) =
20.9 Hz, J (F7,F8) ≈ 19.5 Hz, J (F7,F5) = 8.3 Hz, 1 F, F7), –161.3 (m, J (F8,F7) ≈ 19.5 Hz, J
(F8,F5) = 12.4 Hz, J (F8,F6) = 6.5 Hz, 1 F, F8), –176.2 (m, J (F6,F7) ≈ J (F6,F5) = 20.5 Hz, J
(F6,F8) = 6.5 Hz, 1 F, F6). HRMS (EI): m/z [M-H]+ calcd for C15H8F4NO: 294.0537; found:
294.0536.
4.2.5.17. 5,7,8-Trifluoro-2-phenyl-6-(trifluoromethyl)-2,3-dihydroquinolin-4(1H)-one (9i)
Yellowish solid; yield: 186 mg (54%); Rf = 0.44 (EtOAc/hexane, 1:5, twice); mp 131.2 °C
(decomp.). IR (KBr): 3317, 3035, 2974, 2927, 1678, 1647, 1603, 1523, 1496, 1460, 1346, 1329,
1
1280, 1240, 1176, 1136, 1068, 958, 910, 870, 616, 764, 700, 640, 611, 542, 492, 457 cm–1. H
NMR (300 MHz, Acetone-d6): δ = 7.49 – 7.46 (m, 2 H, Hm), 7.41 – 7.33 (m, 3 H, 2 Ho + Hp),
5.11 (m, 1 H, H2), 3.06 – 2.90 (m, 2 H, H3), 2.82 (s, 1 H, H1). 13C NMR (125 MHz, CDCl3): δ =
24

187.8 (s, C4), 156.1 (dm, 1J (C5,F5) = 273.5 Hz, C5), 150.4 (dm, 1J (C7,F7) = 262.5 Hz, 2J (C7,F8)
= 13.1 Hz, C7), 143.7 (m, C8a), 138.6 (s, C9), 135.1 (dm, 1J (C8,F8) = 241.3 Hz, 2J (C8,F7) = 14.9
Hz, C8), 129.1 (s, C11), 128.9 (s, C12), 126.2 (s, C10), 121.4 (q, 1J (CF3,F) = 270.9 Hz, CF3), 105.0
2
19
(dm, J (C4a,F5) = 11.2 Hz, C4a), 96.9 (m, C6), 56.8 (s, C2), 45.9 (s, C3). F NMR (282 MHz,
Acetone-d6): δ = –53.6 (t, J (CF3,F5) ≈ J (CF3,F7) = 22.1 Hz, 3 F, CF3), –115.8 (qm, J (F5,CF3) =
21.6 Hz, J (F5,F8) = 13.5 Hz, 1 F, F5), –133.2 (m, J (F7,CF3) = 21.6 Hz, J (F7,F8) = 19.0 Hz, 1 F,
F7), –162.6 (m, J (F8,F7) = 19.0 Hz, J (F8,F5) = 13.5 Hz, 1 F, F8). HRMS (EI): m/z [M-H]+ calcd
for C16H8F6NO: 344.0505; found: 344.0510.
4.2.6. 2,3,4,9,10,11-Hexafluoro-7-methyl-6-phenyl-5,6-dihydrodibenzo[b,h][1,6]naphthyridine
(10)
To a solution of 9d (138 mg, 0.5 mmol) in toluene (10 mL), 1-(2-amino-3,4,5-
trifluorophenyl)ethanone (94 mg, 0.5 mmol), p-TSA monohydrate (190 mg, 1.0 mmol) and
MgSO4 (360 mg, 3.0 mmol) were added, and the mixture was heated at reflux for 26 h with
stirring. The mixture was allowed to cool to r.t., placed directly onto a chromatography plate
(silica gel), and air-dried. The target product was isolated by TLC with EtOAc/hexane as an
eluent.
Yellowish solid; yield: 45 mg (21%); Rf = 0.47 (EtOAc/hexane, 1:10, 4 times); mp 217.7 °C
(decomp.). IR (KBr): 3408, 1647, 1574, 1510, 1468, 1396, 1338, 1286, 1265, 1199, 1171, 1107,
1
1041, 1016, 974 920, 868, 843, 767, 702, 555 cm–1. H NMR (300 MHz, Acetone-d6): δ = 8.11
(m, J (H16,F17) = 13 Hz, 1 H, H16), 7.87 (m, J (H3,F4) = 12 Hz, J (H3,F5) = 8 Hz,1 H, H3), 7.24 (s,
13
5 H, Har), 6.63 (s, 1 H, NH), 6.24 (d, 1 H, H9), 2.57 – 2.52 (m, 3 H, H21). C NMR (125 MHz,
1
2
Acetone-d6): δ = 150.4 (dm, J (C17,F17) = 248.8 Hz, J (C17,F18) = 12.3 Hz, C17), 148.9 (s, C7),
146.7 (dm, 1J (C19,F19) = 256.5 Hz, 2J (C19,F18) = 9.0 Hz, C19), 144.3 (dm, 1J (C4,F4) = 237 Hz, 2J
(C4,F5) = 9.6 Hz, C4), 143.4 (s, C10), 142.7 (dm, J (C18,F18) = 252.2 Hz, 2J (C18,F17) = 16.9 Hz,
1
2J (C18,F19) = 14.6 Hz, C18), 142.4 (s, C20), 141.3 (dm, J (C5,F5) = 252.4 Hz, J (C5,F6) = 19.0
1
2
Hz, 2J (C5,F4) = 13.4 Hz, C5), 140.3 (dm, 1J (C6,F6) = 243.2 Hz, 2J (C6,F5) = 13.6 Hz, C6), 136.5
(dm, J (C14,F19) = 8.4 Hz, C14), 133.3 (t, 2J (C1,F6) = 7 Hz, C1), 129.7 (s, C12), 129.7 (s, C12),
2
128.8 (s, C13), 128.6 (s, C8), 127.7 (s, C11), 125.3 (d, J (C15,F17) = 9.0 Hz, C15), 117.0 (m, C2),
3
108.8 (dm, J (C3,F4) = 20.7 Hz, C3), 106.1 (dd, J (C16,F17) = 19.0 Hz, C16), 56.2 (s, C9), 14.3
(m, C21). 19F NMR (282 MHz, Acetone-d6): δ = –134.1 (m, J (F17,F18) ≈ 20 Hz, J (F17,H16) ≈ 12.5
Hz, 1 F, F17), –146.0 (dm, J (F19,F18) = 17.1 Hz, 1 F, F19), –150.2 (m, J (F4,F5) ≈ 19 Hz, J (F4,H3)
≈ 12.5 Hz, 1 F, F4), –157.5 (m, J (F18,F17) = 20.3 Hz, J (F18,F19) = 17.1 Hz, J (F18,H16) = 8.0 Hz,
1 F, F18), –157.4 – –157.9 [m, J (F5,F4) ≈ 19 Hz, 2 F, F5 + F6). HRMS (EI): m/z [M-H]+ calcd for
C23H13F6N2: 431.0977; found: 431.0965.
2
2
Acknowledgments
The authors thank the Russian Foundation for Basic Research (grant № 19-53-53003) for
financial support and the Chemical Service Center SB RAS for spectral and analytical
measurements.
25

References
[1] L.V. Politanskaya, G.A. Selivanova, E.V. Panteleeva, E.V. Tretyakov, V.E. Platonov, P.V.
Nikul'shin, A.S. Vinogradov, Ya.V. Zonov, V.M. Karpov, T.V. Mezhenkova, A.V.
Vasilyev, A.B. Koldobskii, O.S. Shilova, S.M. Morozova, Ya.V. Burgart, E.V.
Shchegolkov, V.I. Saloutin, V.B. Sokolov, A.Yu. Aksinenko, V.G. Nenajdenko, M.Yu.
Moskalik, V.V. Astakhova, B.A. Shainyan, A.A. Tabolin, S.L. Ioffe, V.M. Muzalevskiy,
E.S. Balenkova, A.V. Shastin, A.A. Tyutyunov, V.E. Boiko, S.M. Igumnov, A.D. Dilman,
N.Yu. Adonin, V.V. Bardin, S.M. Masoud, D.V. Vorobyeva, S.N. Osipov, E.V. Nosova,
G.N. Lipunova, V.N. Charushin, D.O. Prima, A.G. Makarov, A.V. Zibarev, B.A. Trofimov,
L.N. Sobenina, K.V. Belyaeva, V.Ya. Sosnovskikh, D.L. Obydennov, S.A. Usachev,
Organofluorine chemistry: promising growth areas and challenges, Russ. Chem. Rev. 88
(2019) 425–569. DOI: https://doi.org/10.1070/RCR4871.
[2] (a) Q.A. Huchet, B. Kuhn, B. Wagner, N.A. Kratochwil, H. Fischer, M. Kansy, D. Zimmerli,
E.M. Carreira, K. Muller, Fluorination patterning: a study of structural motifs that impact
physicochemical properties of relevance to drug discovery, J. Med. Chem. 58 (2015) 9041–
9060.
(b) B. Jeffries, Z. Wang, J. Graton, S.D. Holland, T. Brind, R.D.R. Greenwood, J.-Y. Le
Questel, J.S. Scott, E. Chiarparin, B. Linclau, Reducing the lipophilicity of perfluoroalkyl
groups by CF2−F/CF2−Me or CF3/CH3 exchange, J. Med. Chem. 61 (2018) 10602–10618.
(c) Y. Zafrani, G. Sod-Moriah, D. Yeffet, A. Berliner, D. Amir, D. Marciano, S. Elias, S.
Katalan, N. Ashkenazi, M. Madmon, E. Gershonov, S. Saphier, CF2H, A functional group-
dependent hydrogen-bond donor: is it a more or less lipophilic bioisostere of OH, SH, and
CH3? J. Med. Chem. 62 (2019) 5628–5637.
(d) S. Purser, P.R. Moore, S. Swallow, V. Gouverneur, Fluorine in medicinal chemistry,
Chem. Soc. Rev. 37 (2008) 320–330.
[3] J. Lei, L.B. Su, K. Zeng, T.Q. Chen, R.H. Qiu, Y.B. Zhou, C.T. Au, S.-F. Yin, Recent
advances of catalytic processes on the transformation of alkynes into functional compounds,
Chem. Eng. Sci. 171 (2017) 404−425.
[4] R. Chinchilla, C. Najera, Chemicals from alkynes with palladium catalysts, Chem. Rev. 114
(2014) 1783–1826.
[5] F. Alonso, I.P. Beletskaya, M. Yus, Transition-metal-catalyzed addition of heteroatom-
hydrogen bonds to alkynes, Chem. Rev. 104 (2004) 3079–3159.
[6] S. Derien, P.H. Dixneuf, The versatility of molecular ruthenium catalyst
RuCl(COD)(C5Me5), J. Organometal. Chem. 689 (2004) 1382–1392.
[7] T. Fujihara, K. Semba, J. Terao, Y. Tsuji, Regioselective transformation of alkynes catalyzed
by a copper hydride or boryl copper species, Catal. Sci. Technol. 4 (2014) 1699–1709.
[8] S. Liu, H. Liu, H. Zhou, Q. Liu, J. Lv, Transformation of alkynes into chiral alcohols via
TfOH-catalyzed hydration and Ru-catalyzed tandem asymmetric hydrogenation, Org. Lett.
20 (2018) 1110−1113.
[9] S. Wang, C. Miao, W. Wang, Z. Lei, W. Sun, A salen–Co3+ catalyst for the hydration of
terminal alkynes and in tandem catalysis with Ru–TsDPEN for the one-pot transformation
of alkynes into chiral alcohols, Chem. Cat. Chem. 6 (2014) 1612–1616.
[10] J. Li, C. Wang, D. Xue, Y. Wei, J. Xiao, One-pot transformation of alkynes into alcohols
and amines with formic acid, Green Chem. 5 (2013) 2685–2689.
26

[11] T. Wei, Y. Zeng, W. He, L. Geng, L. Hong, A facile transformation of alkynes into -amino
ketones by an N-bromosuccinimide-mediated one-pot strategy, Chin. Chem. Lett. 30 (2019)
383–385.
[12] H.-T. Qin, X. Xu, F. Liu, Aerobic oxidation of alkynes to 1,2-diketones by organic
photoredox catalysis, Chem. Cat. Chem. 9 (2017) 1409–1412.
[13] C. Qin, P. Feng, Y. Ou, T. Shen, T. Wang, N. Jiao, Selective Csp2–Csp bond cleavage: the
nitrogenation of alkynes to amides, Angew. Chem. Int. Ed. 52 (2013) 7850–7854.
[14] N. Okamoto, M. Ishikura, R. Yanada, Cleavage of carbon – carbon triple bond: direct
transformation of alkynes to nitriles, Org. Lett. 15 (2013) 2571–2573.
[15] L.L. Santos, V.R. Ruiz, M.J. Sabater, A. Corma, Regioselective transformation of alkynes
into cyclic acetals and thioacetals with a gold(I) catalyst: comparison with BrØnsted acid
catalysts, Tetrahedron 64 (2008) 7902–7909.
[16] G. Evano, K. Jouvin, A. Coste, General amination reactions for the synthesis of ynamides,
Synthesis 45 (2013) 17–26.
[17] K. Mochizuki, K. Sakai, T. Kochi, F. Kakiuchi, Rhodium-catalyzed dimerization of
arylacetylenes, Synthesis 45 (2013) 2088–2092.
[18] K.K. Rajbongshi, D. Hazarika, P. Phukan, TsNBr2 mediated oxidative functionalization of
alkynes, Tetrahedron 72 (2016) 4151–4158.
[19] D.-Q. Chen, C.-H. Guo, H.-R. Zhang, D.-P. Jin, X.-S. Li, P. Gao, X.-X. Wu, X.-Y. Liu, Y.-
M. Liang, A metal-free transformation of alkynes directed by remote OH group, Green
Chem. 18 (2016) 4176–4180.
[20] L. Hintermann, A. Labonne, Catalytic hydration of alkynes and its application in Synthesis,
Synthesis 8 (2007) 1121–1150.
[21] D. Hazarika, P. Phukan, Metal free synthesis of quinoxalines from alkynes via a cascade
process using TsNBr2, Tetrahedron 73 (2017) 1374–1379.
[22] L. Politanskaya, E. Tretyakov, p-Toluenesulfonic acid induced conversion of fluorinated
trimethylsilylethynylanilines into aminoacetophenones: versatile precursors for the synthesis
of benzoazaheterocycles, Synthesis 50 (2018) 555–564.
[23] L. Politanskaya, T. Rybalova, O. Zakharova, G. Nevinsky, E. Tretyakov, p-Toluenesulfonic
acid mediated one-pot cascade synthesis and cytotoxicity evaluation of polyfluorinated 2-
aryl-2,3-dihydroquinolin-4-ones and their derivatives, J. Fluorine Chem. 211 (2018) 129–
140.
[24] L. Politanskaya, I. Bagryanskaya, E. Tretyakov, Synthesis of polyfluorinated
arylhydrazines, arylhydrazones and 3-methyl-1-aryl-1H-indazoles, J. Fluorine Chem. 214
(2018) 48–57.
[25] L.V. Politanskaya, I.P. Chuikov, E.V. Tretyakov, V.D. Shteingarts, L.P. Ovchinnikova,
O.D. Zakharova, G.A. Nevinsky, An effective two-step synthesis, fluorescent properties,
antioxidant activity and cytotoxicity evaluation of benzene-fluorinated 2,2-dimethyl-2,3-
dihydro-1H-quinolin-4-ones, J. Fluorine Chem. 178 (2015) 142–153.
[26] L.V. Politanskaya, I.P. Chuikov, V.D. Shteingarts, Synthesis of indoles with a
polyfluorinated benzene ring, Tetrahedron 69 (2013) 8477–8486.
[27] L.V. Politanskaya, V.D. Shteingarts, E.V. Tretyakov, General and efficient synthesis of
polyfluorinated 2-aminotolans and 2-arylindoles, J. Fluorine Chem. 188 (2016) 85–98.
27

[28] L. Politanskaya, V. Shteingarts, E. Tretyakov, A. Potapov. The p-toluenesulfonic acid-
catalyzed transformation of polyfluorinated 2-alkynylanilines to 2-aminoarylketones and
indoles, Tetrahedron Lett. 56 (2015) 5328–5332.
[29] O. Zakharova, G. Nevinsky, L. Politanskaya, D. Baev, L. Ovchinnikova, E. Tretyakov,
Evaluation of antioxidant activity and cytotoxicity of polyfluorinated diarylacetylenes and
indoles toward human cancer cells, J. Fluorine Chem. 226 (2019) 109353
doi.org/10.1016/j.jfluchem.2019.109353.
[30] L.V. Politanskaya, I.P. Chuikov, E.A. Kolodina, M.S. Shvartsberg, V.D. Shteingarts,
Synthesis of polyfluorinated ortho-alkynylanilines, J. Fluorine Chem. 135 (2012) 97–107.
[31] M. Bhanuchandra, M.R. Kuram, A.K Sahoo, Silver(I)-catalyzed reaction between pyrazole
and propargyl acetates: stereoselective synthesis of the scorpionate ligands (E)-allyl-gem-
dipyrazoles (ADPs), J. Org. Chem. 78 (2013) 11824–11834.
[32] N. Chaisan, W. Kaewsri, C. Thongsornkleeb, J. Tummatorn, S. Ruchirawat, PtCl4-catalyzed
cyclization of N-acetyl-2-alkynylanilines: a mild and efficient synthesis of N-acetyl-2-
substituted indoles, Tetrahedron Lett. 59 (2018) 675–680.
[33] G. Sun, F. Cheng, R. Tao, Y. Sun, J. Pan, Y. Zhu, Z. Wang, F. Wu, Y. Yin, Superacid-
catalyzed tandem Meyer–Schuster rearrangement/ intramolecular hydroamination of o-
anilinopropargyl alcohols for the synthesis of 2,3-dihydro-4(1H)-quinolones, Synt. Comm.
46 (2016) 1249–1256.
[34] C. Derabli, S. Mahdjoub, R. Boulcina, B. Boumoud, H. Merazig, A. Debache, [C8dabco]Br:
a mild and convenient catalyst for intramolecular cyclization of 2-aminochalcones to the
corresponding 2-aryl-2,3-dihydroquinolin-4(1H)-ones, Chem. Heterocycl. Comp. 52 (2016)
99–103.
28