TfOH-Promoted Reaction of 2,4-Diaryl-1,1,1-Trifluorobut-3-yn-2-oles with Arenes: Synthesis of 1,3-diaryl-1-CF3-indenes and versatility of the reaction mechanisms

Article abstract of DOI:10.3390/molecules23123079

The TfOH-mediated reactions of 2,4-diaryl-1,1,1-trifluorobut-3-yn-2-oles (CF3-substituted diaryl propargyl alcohols) with arenes in CH2Cl2 afford 1,3-diaryl-1-CF3-indenes in yields up to 84%. This new process for synthesis of such CF3-indenes is complete

Full text of DOI:10.3390/molecules23123079

Article
TfOH-Promoted Reaction of 2,4-Diaryl-1,1,1-
Trifluorobut-3-yn-2-oles with Arenes: Synthesis of
1,3-Diaryl-1-CF
3
-Indenes and Versatility of the
Reaction Mechanisms
1
1
1
2
Aleksey V. Zerov , Anna N. Kazakova , Irina A. Boyarskaya , Taras L. Panikorovskii , Vitalii
3
3
1,4,
V. Suslonov , Olesya V. Khoroshilova and Aleksander V. Vasilyev
*
1
Department of Organic Chemistry, Institute of Chemistry, Saint Petersburg State University,
Universitetskaya nab., 7/9, Saint Petersburg 199034, Russia; lfdse@mail.ru (A.V.Z.);
a.kazakova0@gmail.com (A.N.K.); iralbo@yahoo.com (I.A.B.)
2
3
4
Department of Crystallography, Institute of Earth Sciences, Saint Petersburg State University,
Universitetskaya nab., 7/9, Saint Petersburg 199034, Russia; taras.panikorovsky@spbu.ru
Center for X-ray Diffraction Studies, Research park, St. Petersburg State University, Universitetskiy pr. 26,
Saint Petersburg, Petrodvoretz198504, Russia; v.suslonov@spbu.ru (V.V.S.); o_khorosh@mail.ru (O.V.K.)
Department of Chemistry, Saint Petersburg State Forest Technical University, Institutsky per., 5, Saint
Petersburg 194021, Russia
* Correspondence: aleksvasil@mail.ru; Tel.: +07-812-670-9352; Fax: +07-812-670-9390
Academic Editor: Igor V. Alabugin
Received: 5 November 2018; Accepted: 17 November 2018; Published: 25 November 2018
Abstract: The TfOH-mediated reactions of 2,4-diaryl-1,1,1-trifluorobut-3-yn-2-oles (CF -substituted
3
diaryl propargyl alcohols) with arenes in CH
This new process for synthesis of such CF -indenes is complete at room temperature within one
hour. The synthetic potential, scope, and limitations of this reaction were illustrated by more than
70 examples. The proposed reaction mechanism invokes the formation of highly reactive CF
2
Cl
2
afford 1,3-diaryl-1-CF
3-indenes in yields up to 84%.
3
3
-
propargyl cation intermediates that can be trapped at the two mesomeric positions by the
intermolecular nucleophilic attack of an arene partner with a subsequent intramolecular ring
closure.
Keywords: trifluoromethyl propargyl alcohols; trifluoromethyl indenes; triflic acid; propargyl
cations; cationic reaction mechanism
1. Introduction
Acetylene compounds are of great importance for chemistry, biology, medicine, materials
science, and other fields of science and technology [1–11]. Fluorinated acetylene derivatives are useful
building blocks in organic synthesis for the preparation of new substances and materials with
valuable practical properties. The presence of fluorine atoms in organic compounds gives the
compounds unique characteristics, such as high lipophilicity and biological activity, heat resistance,
nonlinear optical and liquid crystal properties, and so forth [12–16]. Synthesis of new organofluorine
derivatives is an actual goal of modern organic chemistry.
Among the variety of acetylene compounds, propargyl alcohols play an important role in the
synthesis of miscellaneous substances. For instance, they have been widely used in Friedel-Crafts
alkylation catalyzed by Brønsted [17–23] or Lewis [24–35] acids. However, reactions of
trifloromethyl-substituted propargyl alcohols in electrophilic media have not been studied yet.
Molecules 2018, 23, 3079; doi:10.3390/molecules23123079
www.mdpi.com/journal/molecules

Molecules 2018, 23, 3079
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Based on our work on the electrophilic activation of unsaturated compounds (alkynes, alkenes,
allenes) [36], we undertook a special study on the transformation of trifluoromethyl-substituted
propargyl alcohols. The main goal of this work was to investigate reactions of 2,4-diaryl-1,1,1-
trifluorobut-3-yn-2-oles (CF
3
-propargyl alcohols) with arenes under the action of various Brønsted
and Lewis acids.
The starting diaryl-substituted CF
3
-propargyl alcohols 1a–r bearing various substituents in
aromatic rings are shown in Figure 1. They were obtained from the corresponding 1,3-
diarylpropynones by trifluoromethylation-O-trimethylsilylation of the carbonyl group followed by a
desilylation stage (see synthetic procedures in the Supplementary Materials).
Figure 1. Starting CF -propargyl alcohols used in this study.
3
2. Results and Discussion
One may propose several ways of conducting transformations of alcohols 1 in acidic media
(Scheme 1). First, the protonation of the hydroxyl group takes place with the formation of cation A.
Elimination of water from it gives the propargyl cation B, which may be presented as two mesomeric
2
4
forms, B′↔B″, having two electrophilic reactive centers on carbons C and C , respectively. Species
2
A and B′, with their electrophilic center on carbon C , may react with the arene, Ar″H, leading to
alkyne 3 (way a). Protonation of the latter gives rise to the vinyl cation D, which may undergo
cyclization into the aryl groups Ar′ or Ar″, with the formation of indenes 4 or 7, respectively.
Another reaction pathway is the reaction of the arene with species B″ onto its electrophilic
4
carbon C , which affords allene 2. Protonation of the latter gives the mesomeric allyl cation C′↔C″.
Species C′ may be cyclized into both rings Ar″ and Ar, leading to indenes 4 and 5, respectively (way
b). One more possible pathway for this allyl cation is cyclization through its resonance form C″,
giving rise to indene 6 (way c).

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OH
CF3
Ar'
H+
OH2
CF3
Ar'
Ar
Ar
Ar
way a
A
H+
Ar''
CF3
Ar'
1
Ar''
Ar''H
-H+
Ar
-H2O
Ar
CF3
Ar'
-H+
Ar''
D
3
1
CF3
1
CF3
3
2
4
3
-H+
Ar
4
2
B'
Ar'
Ar'
B''
Ar'
R'
R''
CF3
CF3
-H+
Ar''H
Ar
7
Ar
Ar''
CF3
Ar'
Ar
way b
-H+
Ar
H+
4
Ar''
CF3
C'
Ar'
R
CF3
Ar'
2
Ar''
5
Ar''
Ar
Ar
way c
-H+
Ar''
CF3
C''
Ar'
R'
CF3
6
Scheme 1. Plausible mechanisms of acid-promoted reactions of CF3-alcohols 1 with arenes.
To estimate the electronic characteristics of the initial intermediates A and B of these reactions,
DFT (density functional theory) calculations of species Aa and Ba (B′a↔B″a) derived at the
protonation of alcohol 1a were carried out (Table 1). Energies of the HOMO (highest occupied
molecular orbital) and LUMO (lowest unoccupied molecular orbital), charge distribution, the
contribution of the atomic orbitals into the molecular orbital, and the global electrophilicity index ω
[37,38] were calculated. The calculations show that species Ba should be a rather active electrophile,
since it is characterized by a large value of the electrophilicity index ω, of 7.59 e, compared to species
2
Aa, with ω of 3.92 e. The cation Aa has a large positive charge of 1.00 e on carbon C . This carbon
2
gives a large contribution into the LUMO of 13.2%. This proves that carbon C in the species Aa is an
electrophilic reactive center according to both charge and orbital factors.
4
Contrary to that, the cation Ba has a larger positive charge, of 0.23, on carbon C . However,
2
carbon C gives a larger contribution into the LUMO, of 28.5%. This suggests that in this species, the
4
2
electrophilic reactivity of the atom C is ruled under charge control, but the reactivity of the atom C
may be explained by orbital control.
Table 1. Selected electronic characteristics (DFT calculations) of cations Aa and Ba (B′a↔B″a) derived
at the protonation of alcohol 1a.
a
2
b
4
b
2
с
4
с
EHOMO,
eV
ELUMO,
eV
ω ,
q(C ) ,
e
q(C ) ,
e
k(C )LUMO ,
k(C )LUMO ,
Caption
OH2
eV
%
%
4
3
2
−7.40
−3.57
−5.03
3.92
1.00
−0.34
13.2
28.5
9.4
Ph
Ph
CF3
1
Aa
Ph
1
CF3
2
Ph
−7.69
7.59
0.043
0.23
19.9
4
3
Ba (B'a
B''a)
a Global electrophilicity index ω = (EHOMO + ELUMO)2/8(ELUMO−EHOMO). b Natural charges. c Contribution
of the atomic orbital into the molecular orbital.
Thus, there are three main pathways, a, b, and c, for the reactions of CF3-propargyl alcohols with
arenes, proceeding through various cationic intermediates which may lead to various CF3-indenes

Molecules 2018, 23, 3079
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(Scheme 1). A key point in this reaction mechanism is a possible dual reactivity of propargyl cations
B (B′↔B″), which may finally lead to different indene structures.
To determine the dependence of the reaction pathway on the substituents in the aromatic rings
in alcohols 1 and arenes, starting substrates containing various donor and acceptor substituents in
aryl moieties were investigated in these reactions.
First, we conducted reactions of alcohol 1a with benzene under the action of different Brønsted
and Lewis acids (Table 2). In all cases, indene 4aa was obtained. However, a better result with the
highest yield of 4aa was achieved for the reaction with the use of 1.5 equivalents of
trifluoromethanesulfonic acid СF3SO3H (triflic acid, TfOH) at room temperature for 1 h (entry 3, Table
2).
Table 2. Acid-promoted reaction of 1a with benzene.
F3C
Ph
CF3
acid
OH +
Ph
Ph
1a
4aa
Ph
a
b
Reaction Conditions
Yield of 4аa,
Entry
%
30
45
57
44
40
33
40
Acid
TfOH (50 eq.)
TfOH (50 eq.)
TfOH (1.5 eq.)
FSO3H (86 eq.)
H2SO4 (5 eq.)
AlCl3 (2 eq.)
Temperature, °C
Time, h
1
2
3
4
5
6
7
8
9
r.t.
−35
r.t.
−75
r.t.
r.t.
r.t.
r.t.
85
1
1
1
1
1
1
1
72
1
1
c
c
FeCl3 (1 eq.)
d
BF3 × Et2O (2 eq.)
Sc(OTf)3 (0.1 eq.)
Cu(OTf)2 (0.1 eq.)
27
42
30
e
e
10
85
a Reaction conditions: acid, solvent CH2Cl2, molar ratio of 1:benzene = 1:50. b Complete conversion of
1а. c Cosolvent was CH2Cl2. d Conversion of 1а was 60%. e Cosolvent was 1,2-dichloroethane.r.t. room
temperature.
Maintaining these conditions (1.5 equiv. of TfOH, r.t., 1 h), we conducted reactions of other
alcohols 1 with various arenes, benzene (Table 3), ortho-xylene (Scheme 2), para-xylene (Table 4),
meta-xylene (Table 5), pseudocumene (1,2,4-trimethylbenzene, Table 6), and veratrole (1,2-
dimethoxybenzene, Table 7). These reactions led to compounds 3, 4, 5, and 6. Structures of these
1
13
19
substances were determined by means of H, C, and F-NMR, HRMS, and X-ray single crystal
structure analysis (see Figure 2).
In principle, the structures of the target indenes 4, 5, and 6 reveal the reaction pathway of their
formation (ways a, b, c in Scheme 1) and key intermediates of these transformations (A, B, C, and D
in Scheme 1). These data are shown in Tables 3–7 for every reaction. In some cases, it is not possible
to unequivocally distinguish the reaction pathways based only on the structures of the compounds
obtained. However, many reactions clearly point out the mechanism of the formation of the final
products.
The data in Table 3 show that for alcohols 1 having phenyl or aryl rings with acceptor groups at
the acetylene bond, the only reaction products are indenes of the general structure 4a, obtained as a
result of cyclization into a phenyl ring (entries 1–3, 5–8, 12–14, 17, and 18). These compounds may be
formed via pathway a or b (Scheme 1).
Alcohols 1 bearing donor methyl groups in the aryl substituent at the triple bond react with
benzene to form a mixture of indenes of types of 4a and 5a. The latter is the main reaction product

Molecules 2018, 23, 3079
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(entries 9–11). Compounds 5a are formed at the cyclization into the electron-rich aryl ring (not into
4
the phenyl one) at carbon C in cations C (way a, Scheme 1).
2
Alcohol 1d, with a 3,4-dimethylphenyl ring at carbon C , additionally gave indenes 6a and 6b,
which were formed by way c only (see Scheme 1).
Table 3. TfOH-promoted reaction of alcohols 1a–f with benzene; reaction conditions: TfOH, CH2Cl2,
molar ratio of 1:benzene:TfOH = 1:50:1.5, room temperature, 1 h.
R'
R'
CF3
CF3
CF3
TfOH (1.5 eq.),
CH2Cl2
R'
OH
CF3
R'
+
R
R
r.t., 1h
1
R
4a
5a
6
R
Possible Reaction
Way and
Intermediates
from Scheme 1
Reaction Products 4a, 5a, and 6
(Yield, %, Ratio of Isomers)
Entry
Alcohol
way а: A (or B′), D
way b: B″, C′
1
2
1а
4aa (57%)
way b: B″, C′
way b: B″, C′
1b
4ab (48%)
Me
F3C
3
4
1c
Ph
4ac (69%)
4ad—way b: B″, C′
6a, 6b—way c: B″,
C″
4ad
CF3
Me
Me
1d
Ph
Ph
6a
6b
total yield of 47% (4ad:6a:6b = 5:2:1)
way а: A (or B′), D
way b: B″, C′
5
6
1e
1f
4ae (73%)
4af (80%)
way а: A (or B′), D
way b: B″, C′

Molecules 2018, 23, 3079
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way а: A (or B′), D
7
way b: B″, C′
1g
4ag (66%)
4ah (70%)
way а: A (or B′), D
way b: B″, C′
8 a
1h
way а: A (or B′), D
way b: B″, C′
9
1i
4ai
5aa
total yield of 72% (4ai:5aa = 1:3.8)
way а: A (or B′), D
way b: B″, C′
10
1j
4aj
5ab
total yield of 47% (4aj:5ab = 1:7)
11
12
way b: B″, C′
5ac (31%)
5ad (19%)
1k
1l
way а: A (or B′), D
way b: B″, C′
4ak (59%)
way а: A (or B′), D
way b: B″, C′
13
1m
1n
4al (51%)
way а: A (or B′), D
way b: B″, C′
14 a
4am (62%)
15
Complex mixture of reaction products
-
1o

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16
Complex mixture of reaction products
-
1p
1q
way а: A (or B′), D
way b: B″, C′
17
18
4an (70%)
4ao (80%)
way а: A (or B′), D
way b: B″, C′
1r
a Amount of TfOH was 2.5 equiv.
Alcohol 1a in reaction with o-xylene afforded indene 5ac (Scheme 2). Again, one may propose
two possible directions for the formation of this compound: way a or b (see Scheme 1).
F3C
Ph
Me
Me
Me
Me
CF3
OH
Ph
TfOH, CH2Cl2
r.t., 1h
+
Ph
1a
Ph
5ac (48%)
Scheme 2. TfOH-promoted reaction of 1 with o-xylene in TfOH; reaction conditions: TfOH, CH2Cl2,
molar ratio of 1:benzene:TfOH = 1:1.1:1.5, room temperature, 1 h.
In almost all cases for the reactions of alcohols 1 with p-xylene, indenes of the general structure
4b were obtained (Table 4). These compounds may be formed by way a through the vinyl cation D or
way b through the cation C′ (Scheme 1).
Table 4. TfOH-promoted reaction of 1 with p-xylene; reaction conditions: TfOH, CH2Cl2, molar ratio
of 1:p-xylene:TfOH = 1:1.1:1.5, room temperature, 1 h.
R'
CF3
R'
CF3
Me
Me
R
Me
Me
TfOH (1.5 eq.),
CH2Cl2
R'
OH
CF3
r.t., 1h
Me
R
1
5b
4b
Me
R
Possible Reaction Way
and Intermediates from
Scheme 1
Reaction Products 4 and 5
(Yield, %, Ratio of Isomers)
Entry
Alcohol
way а: A (or B′), D
way b: B″, C′
1
1а
4ba (75%)

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2
way b: B″, C′
1b
4bb (66%)
4bс (44%)
4bd (72%)
way а: A (or B′), D
way b: B″, C′
3
4
1с
way b: B″, C′
1d
way а: A (or B′), D
way b: B″, C′
5
6
1e
1f
4be (60%)
way а: A (or B′), D
way b: B″, C′
4bf (74%)
4bg (45%)
way а: A (or B′), D
way b: B″, C′
7
1g
way а: A (or B′), D
way b: B″, C′
8 а
1h
4bh (84%)
way а: A (or B′), D
way b: B″, C′
9
1i
4bi (71%)
Me
F3C
Ph
Me
Me
10
way b: B″, C′
Me
1k
4bj
5ba
total yield of 28% (4bj:5ba = 1.5:1)

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5bb (34%)
way а: A (or B′), D
11
12
way b: B″, C′
1l
4bk (68%)
way а: A (or B′), D
way b: B″, C′
1m
1n
4bl (58%)
way а: A (or B′), D
way b: B″, C′
13 а
4bm (70%)
way а: A (or B′), D
way b: B″, C′
14
1o
4bn (59%)
4bo
5bc
15
way b: B″, C′
total yield of 25% (4bo:5bc = 1.4:1)
1p
5bd (25%)
way а: A (or B′), D
way b: B″, C′
16
1q
4bp (74%)

Molecules 2018, 23, 3079
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way а: A, B′, D
way b: B″, C′
17
1r
4bq (78%)
a Amount of TfOH was 2.5 equiv.
Additional proof for the proceeding of the reaction of alcohol 1n with p-xylene in way b was the
isolation of allene 2a, which then was transformed into indene 4bm in TfOH.
O2N
Me
TfOH (1.5 eq.),
CH2Cl2
TfOH (1.5 eq.),
CH2Cl2
CF3
Ph
CF3
OH
Ph
4bm
+
O2N
r.t., 1h
r.t., 1h
1n
Me
Me
Me
2a
TfOH (2.5 eq.), CH2Cl2
r.t., 1h
Scheme 3. TfOH-promoted reaction of 1n with p-xylene in TfOH.
Based on the structure of the reaction products 4c and 5c obtained from alcohols 1 and m-xylene
(Table 5), one may assume that in all cases, the m-xylene molecule is attacked by the electrophilic
4
center C of species B″, which leads to the formation of the corresponding indenes in way b (Scheme
4
1). The presence of electron-withdrawing substituents in the aryl ring at the atom C prevents
electrophilic substitution into this ring, and only indenes 4ci–4cm were isolated (entries 10–12, 15,
16).
Table 5. TfOH-promoted reaction of 1 with m-xylene; reaction conditions: TfOH, CH2Cl2, molar ratio
of 1:m-xylene:TfOH = 1:1.1:1.5, room temperature, 1 h.
R'
CF3
R'
CF3
Me
TfOH (1.5 eq.),
CH2Cl2
Me
R'
R
OH
CF3
r.t., 1h
R
Me
Me
Me
1
5c
4c
R
Me
Possible Reaction Way and
Intermediates from
Scheme 1
Reaction Products 4 and 5 (Yield,
%, Ratio of Isomers)
Entry
Alcohol
1
way b: B″, C′
1а
4aj
5ab
total yield of 63% (4aj:5ab = 6:1)

Molecules 2018, 23, 3079
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2
way b: B″, C′
1b
4ca
5ca
total yield of 66% (4ca:5ca = 3:1)
3
way b: B″, C′
1c
1d
1e
4cb
5cb
total yield of 69% (4cb:5cb = 6:1)
4
5
way b: B″, C′
4cc
5cc
total yield of 69% (4cc:5cc = 5.7:1)
way b: B″, C′
4cd
5cd
total yield of 60% (4cd:5cd = 4:1)
Br
F3C
Me
6
way b: B″, C′
1f
Ph
Me
4ce
5ce
total yield of 56% (4ce:5ce = 4.9:1)
7
way b: B″, C′
way b: B″, C′
1g
4cf (40%)
8 а
1h
4cg (54%)

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9
way b: B″, C′
way b: B″, C′
1i
1l
4ch
5cf
total yield of 56% (4ch:5cf = 2.8:1)
10
4ci (63%)
4cj (58%)
11
way b: B″, C′
way b: B″, C′
1m
1n
12 а
4ck (63%)
Complex mixture of reaction
products
13
14
-
-
1o
Complex mixture of reaction
products
1p
15
16
way b: B″, C′
way b: B″, C′
1q
4cl (64%)
1r
4cm (50%)
a Amount of TfOH was 2.5 equiv.
Reactions of alcohols 1 with electron-rich pseudocumene afforded two types of indene
structures, 4d and 4e, formed by electrophilic substitution onto the pseudocumene moiety only (Table
6). Taking into account that the most active position for electrophilic attack in the pseudocumene
5
molecule is the atom C and that the first reaction occurs in this particular position, one may propose
that indenes 4da–do are formed in way b through cations B″ and C′, and indenes 4ea–4eo in way a
through cations A (or B′) and D (see Scheme 1). The structures of compounds 4d and 4e and positions

Molecules 2018, 23, 3079
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of the methyl groups in the indene core were determined by H,H and H,F NOESY correlations
between the methyl substituents, CF3 group, and aromatic indene protons (see the Supporting
Information).
Table 6. TfOH-promoted reaction of 1 with pseudocumene; reaction conditions: TfOH, CH2Cl2, molar
ratio of 1:pseudocumene:TfOH = 1:1.1:1.5, room temperature, 1 h.
R'
R'
Me
Me
Me
CF3
CF3
Me
Me
Me
TfOH (1.5 eq.),
CH2Cl2
R'
OH
CF3
Me
r.t., 1h
Me
R
Entry
1
Me
1
4e
4d
R
R
Possible Reaction Way
and Intermediates from
Scheme 1
Reaction Products 4d and 4e
(Yield, %, Ratio of Isomers)
Alcohol
4da—way b: B″, C′
4ea—way а: A (or B′), D
1а
4da
4ea
total yield of 75% (4da:4ea = 11.5:1)
4db—way b: B″, C′
2
3
4eb—way а: A (or B′), D
1b
4db
4eb
total yield of 69% (4db: 4eb = 11.5:1)
4dc—way b: B″, C′
4ec—way а: A (or B′), D
1c
4dc
4ec
total yield of 50% (4dc:4ec = 13:1)
4dd—way b: B″, C′
4
4ed—way а: A (or B′), D
1d
4dd
4ed
total yield of 67% (4dd:4ed = 15.7:1)
4de—way b: B″, C′
4ee—way а: A (or B′), D
5
6
1e
1f
4de
4ee
total yield of 66% (4de:4ee = 11.5:1)
4df—way b: B″, C′
4ef—way а: A (or B′), D
4df
4ef

Molecules 2018, 23, 3079
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total yield of 80% (4df:4ef = 24:1)
4eg—way b: B″, C′
4fg—way а: A (or B′), D
7
1g
4dg
4eg
total yield of 70% (4dg:4eg = 2.7:1)
4dh—way b: B″, C′
4eh—way а: A (or B′), D
8 а
4dh
4eh
1h
total yield of 58% (4dh:4eh = 1.8:1)
4di—way b: B″, C′
4ei—way а: A (or B′), D
9
1i
4di
4ei
total yield of 51% (4di:4ei = 12:1)
10
Complex mixture of reaction products
-
1k
4dj—way b: B″, C′
4ej—way а: A (or B′), D
11
12
13
1l
4dj
4ej
total yield of 54% (4dj:4ej = 11.5:1)
4dk—way b: B″, C′
4ek—way а: A (or B′), D
1m
4dk
4ek
total yield of 49% (4dk:4ek = 10:1)
4dl—way b: B″, C′
4el—way а: A (or B′), D
1nа
4dl
4el
total yield of 66% (4dl:4el = 13:1)
4dm—way b: B″, C′
14
4em—way а: A (or B′), D
1o
4dm
4em

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total yield of 65% (4dm:4em = 6:1)
15
Complex mixture of reaction products
-
1p
1q
4dn—way b: B″, C′
4en—way а: A (or B′), D
16
4dn
4en
total yield of 49% (4dn :4en = 10:1)
4do—way b: B″, C′
4eo—way а: A (or B′), D
17
1r
4do
4eo
total yield of 57% (4do:4eo = 11.5:1)
a Amount of TfOH was 2.5 equiv.
Surprisingly, reactions of alcohols 1 with veratrole yielded mixtures of alkyne 3 and indene 4f.
Moreover, treatment of alkyne 3 with TfOH (1.5 eq.) in CH2Cl2 at room temperature for 1 h gave
indene 4f. This data unambiguously proves that reactions with veratrole proceed in way a with the
participation of cations A (or B′) and D (see Scheme 1).
Table 7. TfOH-promoted reaction of 1 with veratrole; reaction conditions: TfOH, CH2Cl2, molar ratio
of 1:veratrole:TfOH = 1:1.1:1.5, room temperature, 1 h.
R'
TfOH (1.5 eq.),
CH2Cl2
CF3
R'
R'
OMe
OMe
MeO
MeO
OH
CF3
CF3
+
R
r.t., 1h
R
OMe
OMe
1
3
4f
R
Possible Reaction Way
and Intermediates from
Scheme 1
Reaction Products 4f and 3
(Yield, %, Ratio of Isomers)
Entry
Alcohol
way а: A (or B′), D
a
1
1а
4fa
3a
total yield of 60% (4fa: 3a = 2.8:1)

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way а: A (or B′), D
2
1b
4fb
3b
total yield of 49% (4gb:3b = 3.5:1)
way а: A (or B′), D
way а: A (or B′), D
way а: A (or B′), D
way а: A (or B′), D
3
4
5
6
1c
4fc
3c
total yield of 98% (4fc:3c = 4.9:1)
1d
4fd
3d
total yield of 76% (4fd:3d = 5:1)
1e
4fe
3e
total yield of 44% (4fe:3e = 6:1)
1f
4ff
3f
total yield of 70% (4ff:3f = 4:1)
way а: A (or B′), D
a
7
1g
4fg (82%)
8
Complex mixture of reaction products
-
1h

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way а: A (or B′), D
9
1i
4fh
3g
total yield of 54% (4fh:3g = 13:1)
way а: A (or B′), D
a
10
1j
4fi (67%)
way а: A (or B′), D
a
11
1k
4fj (57%)
way а: A (or B′), D
12
1l
4fk
3h
total yield of 65% (4fk:3h = 10:1)
way а: A (or B′), D
13
14
1m
1n
4fl
3i
total yield of 36% (4fl:3i = 7:1)
Complex mixture of reaction products
-

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Me
F3C
MeO
MeO
way а: A (or B′), D
a
15
1o
1p
Me
4fm (69%)
16
Complex mixture of reaction products
-
Cl
F3C
MeO
MeO
Cl
way а: A (or B′), D
OMe
OMe
17
Cl
CF3
1q
Cl
4fn
3j
total yield of 50% (4fn:3j = 2.8:1)
Br
OMe
OMe
F3C
MeO
MeO
Br
CF3
way а: A (or B′), D
18
Br
Br
1r
4fo
3k
total yield of 59% (4fo:3k = 2:1)
a Amount of TfOH was 2.5 equiv.
4bg
4ci
4dc

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4de
4dg
4di
4dk
4dm
4fb
4fc
4fh
4fk
5ac
Figure 2. X-ray crystal structures of compounds 4bg (CCDC 1568593), 4ci (CCDC 1578216), 4dc
(CCDC 1568602), 4de (CCDC 1568599), 4dg (CCDC 1568594), 4di (CCDC 1563374), 4dk (CCDC
1568596), 4dm (CCDC 1568600), 4fb (CCDC 1568595), 4fc (CCDC 1568597), 4fh (CCDC 1568603), 4fk
(CCDC 1568598), and 5ac (CCDC 1568601) (ellipsoid contour of probability levels is 50%), Green sticks
are fluorine atoms.

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Summarizing the data obtained on the TfOH-promoted reactions of CF3-propargyl alcohols 1
with different arenes, leading to CF3-indenes (Tables 3–7), one may conclude that these indenes may
be formed in several reaction pathways (Scheme 1), depending on the structures of the starting
alcohol 1 and the nucleophilicity of the arene. Key intermediates of these reactions are o-protonated
forms A of the alcohols and the mesomeric propargyl cations B (B′↔B″) generated from alcohols 1
in acidic media (see Scheme 1). Most probably, reactions with electron-rich arenes, pseudocumene
(Table 6), and veratrole (Table 7) may proceed through cations A (way a in Scheme 1), which are
sufficiently electrophilic (see data on DFT calculations in Table 2) to react with such donating arenes.
Reactions with other less nucleophilic arenes, benzene, and xylenes (Tables 3–5) may go both in way
a and b (Scheme 1) due to the dual reactivity of the propargyl cation B. However, way b through the
allenyl resonance form B″ may be more preferable; see the reactions with m-xylene that proceed
mainly in this way (Table 5). Construction of the indene core at the final stages of the reaction depends
on the nucleophilicity of the aryl rings Ar, Ar′, and Ar″ in the intermediate species C and D.
Electrophilic cyclization takes place in the more-donating aromatic moiety.
It should be noted that many of the reactions studied lead to the exclusive formation of only one
of CF3-indene 4 or 5 in good yields. Such CF3-indenes are rather rare substrates, and there are only a
few reports on their synthesis [39–44].
3. Conclusions
We have studied, for the first time, reactions of diaryl-substituted CF3-propargyl alcohols with
arenes under the action of the superacid TfOH. The reaction proceeds through the intermediate
formation of several cationic species, which finally lead to the formation of the synthetically hardly
available 1,3-diaryl-1-CF3-indenes.
Supplementary Materials: The following are available online. Experimental procedures, characterization of
compounds, copies of NMR spectra, and data on DFT calculations.
Author Contributions: Conceptualization, A.V.V.; Synthesis of Starting Compounds and Study on Their
Electrophilic Reactions, A.V.Z. and A.N.K.; DFT Study, I.A.B.; X-Ray Study, T.L.P., V.V.S. and O.V.K.; Writing-
Original Draft Preparation, A.V.V.
Funding: This work was supported by the Russian Scientific Foundation (Grant No. 18-13-00008).
Acknowledgments: Spectral studies were performed at the Center for Magnetic Resonance, the Center for
Chemical Analysis and Materials Research, and the Center for X-ray Diffraction Studies, Saint Petersburg,
Russia.
Conflicts of Interest: The authors declare no conflict of interest.
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Sample Availability: Samples of the compounds are available from the authors.
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