Catalytic Synthesis of Trifluoromethylated Allenes, Indenes, Chromenes, and Olefins from Propargylic Alcohols in HFIP

Article abstract of DOI:10.1021/acs.joc.9b02398

A general method to access CF₃-substituted allenes from propargylic alcohols under Lewis acid catalysis in 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) as solvent is described. By tuning the reaction time and temperature, the obtained allenes rearr

Full text of DOI:10.1021/acs.joc.9b02398

Subscriber access provided by Karolinska Institutet, University Library
Article
Catalytic Synthesis of Trifluoromethylated Allenes, Indenes,
Chromenes and Olefins from Propargylic Alcohols in HFIP
Florent Noel, Vuk D. Vukovic, Jing Yi, Edward Richmond, Pavle Kravljanac, and Joseph Moran
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.9b02398 • Publication Date (Web): 19 Nov 2019
Downloaded from pubs.acs.org on November 20, 2019
Just Accepted
“Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted
online prior to technical editing, formatting for publication and author proofing. The American Chemical
Society provides “Just Accepted” as a service to the research community to expedite the dissemination
of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts appear in
full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been fully
peer reviewed, but should not be considered the official version of record. They are citable by the
Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered to authors. Therefore,
the “Just Accepted” Web site may not include all articles that will be published in the journal. After
a manuscript is technically edited and formatted, it will be removed from the “Just Accepted” Web
site and published as an ASAP article. Note that technical editing may introduce minor changes
to the manuscript text and/or graphics which could affect content, and all legal disclaimers and
ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors or
consequences arising from the use of information contained in these “Just Accepted” manuscripts.
is published by the American Chemical Society. 1155 Sixteenth Street N.W.,
Washington, DC 20036
Published by American Chemical Society. Copyright © American Chemical Society.
However, no copyright claim is made to original U.S. Government works, or works
produced by employees of any Commonwealth realm Crown government in the course
of their duties.

Page 1 of 39
The Journal of Organic Chemistry
1
2
3
4
5
6
Catalytic Synthesis of Trifluoromethylated Allenes, Indenes, Chromenes and Olefins from
Propargylic Alcohols in HFIP
7
8
9
Florent Noёl, Vuk D. Vuković, Jing Yi, Edward Richmond, Pavle Kravljanac and Joseph
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Moran*
Université de Strasbourg, CNRS, ISIS, 8 allée Gaspard Monge, 67000 Strasbourg, France
moran@unistra.fr
Abstract
A general method to access CF3-substituted allenes from propargylic alcohols under Lewis acid
catalysis in 1,1,1,3,3,3‐hexafluoro‐2‐propanol (HFIP) as solvent is described. By tuning the
reaction time and temperature, the obtained allenes rearrange to 1,3-biaryl-1-trifluoromethyl-1H-
indenes. By tuning the structure of the propargylic alcohol substrates, a range of
trifluoromethylated 2H-chromenes were successfully synthesized, with use of catalytic quantities
of strong Brønsted acid in HFIP. The present method is therefore highly potent for synthesis of a
number of potentially pharmaceutically interesting new trifluoromethylated compounds and
produces water as the only stoichiometric byproduct.
INTRODUCTION
Propargylic alcohols represent an attractive class of starting compounds for a number of chemical
transformations.1 The direct nucleophilic substitution of propargylic alcohols can result in two
types of products: an α-substituted alkyne or an allene (Scheme 1a).2 The transformations leading
to alkynes are well studied.3 On the other hand, there are few examples of the formation of allenes
from propargyl alcohols through carbocationic intermediates.4 Generally, carbocationic
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 2 of 39
1
2
3
4
5
6
7
8
9
intermediates bearing an adjacent electron-withdrawing group, such as a CF3 group, are difficult
to form. They are typically generated from halides or pseudo-halides.5 In some cases, they have
been generated from alcohols in the presence of superstoichiometric quantities of Brønsted or
Lewis acids.6,7 Catalytic methods for their generation are desirable because substituting hydrogen
atoms for fluorine atoms is well known to modulate a molecule’s physico-chemical and
pharmaceutically relevant properties,8 such as its pharmacokinetics and binding affinity.9 One of
the most suitable organic solvents used to carry out reactions involving short-lived carbocations is
1,1,1,3,3,3-hexafluoroisopropanol (HFIP).10 We recently reported that Brønsted acid catalyzed
Friedel-Crafts reactions of α-trifluoromethylated benzylic alcohols proceed with ease via α-
trifluoromethyl carbocationic species in HFIP.11 As a continuation of this research program, we
explored the reactivity of α-trifluoromethylated propargylic alcohols in HFIP under Brønsted and
Lewis acid catalysis. Here we show that CF3-bearing propargyl alcohols are versatile substrates in
dehydroarylative Friedel-Crafts reactions (Scheme 1b), giving access to a number of
trifluoromethylated allenes, indenes, chromenes and alkenes. The method is of use for the
diversity-oriented synthesis of trifluoromethylated compounds, which are of considerable interest
to pharmaceutical research,12 and produces water as the only stoichiometric byproduct.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Scheme 1. HFIP-assisted transformation of α-CF3 propargyl alcohols.
ACS Paragon Plus Environment

Page 3 of 39
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
Methods for the synthesis of allenes bearing electron-withdrawing groups, such as keto,
carboxy, ester, amide, cyano, sulfone groups have been described.13 Among them, only a limited
number allow access to monoaryl14 and biaryl15 mono(CF3) substituted allenes (Scheme 2a). A
single example of the Pd-catalyzed synthesis of triaryl mono(CF3) substituted allenes in known.16
To our knowledge, no general catalytic methods allowing access to triaryl mono(CF3) substituted
allenes have been reported so far. Furthermore, methods for CF3-allene synthesis proceeding via
carbocationic intermediates have not been described.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Methods for the synthesis of indenes bearing CF3-groups at the C1-C3 positions are known
but are limited in terms of the substitution patterns that can be achieved. Reported strategies
include the treatment of indanones with perfluoroalkyl lithium reagents17 and the use of α-
(trifluoromethyl)allyl alcohols.18,19 In general, indenes can be prepared by the isomerization of
allenes,20 but the preparation of CF3-indenes through the intermediacy of CF3-allenes, reported
herein, had not been described. However, during the preparation of this manuscript, Vasilyev,
Nenajdenko, Krasavin and collaborators reported a single example of the conversion of a
propargylic alcohol to a CF3-indene using neat sulfuric or triflic acid as solvent,21 or zeolites22
under high pressure and temperature conditions (Scheme 2b). Herein we report the first general
method for the synthesis of 1,3-biaryl-1-trifluoromethyl-1H-indenes, which employs a Brønsted
acid catalyzed approach under significantly milder conditions. Moreover, by tuning of the reaction
time and temperature, the corresponding intermediate triaryl CF3 allenes can be accessed.
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 4 of 39
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Scheme 2. Previous reports on CF3-allene and -indene synthesis
RESULTS AND DISCUSSION
Reaction discovery and optimization. We began our investigations with standard conditions for
dehydroarylative reactions of benzylic alcohols in HFIP that were previously established.11 Instead
of direct nucleophilic substitution on the α-CF3 carbon of alcohol 1, with TfOH as catalyst in HFIP
at room temperature we observed the nucleophile attack on γ-carbon and formation of allene 1a
o
(Table 1, entry 1). When the same reaction is conducted at higher temperature (50 C), the
formation of an additional product (CF3-substituted indene, 2a) was observed (entry 2). Weaker
Brønsted acids did not lead to the formation of allene or indene (entries 3-5). The stronger
fluoroantimonic acid gave a mixture of allene and indene in an approximate ratio of 11:1 (entry
6). Some Lewis acid catalysts provided the allene, but not the corresponding indene in significant
yield (entries 7-11). However, FeCl3 led to the formation of the allene in 93% isolated yield in 10
min (entry 12). Heating at 80 oC after longer reaction times led to complete transformation to the
corresponding indene (entry 13). By testing the same reaction in other solvents (entries 14-16),
we confirmed that this reactivity is optimal in HFIP. Iron(II) chloride was not as efficient as
iron(III) chloride (entry 17).
ACS Paragon Plus Environment

Page 5 of 39
The Journal of Organic Chemistry
1
2
3
4
5
6
Table 1. Reaction optimization and discovery
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
yield 1a
(%)
85
50
60
-
traces
87
9
66
24
7
69
93
-
-
39
9
yield 2a
(%)
-
43
-
-
-
8
-
-
10
-
-
-
94
-
-
-
-
entry catalyst
solvent
time
1
TfOH
TfOH
TFA
H3PO4
HClb
HFIP
HFIP
HFIP
HFIP
HFIP
HFIP
HFIP
HFIP
HFIP
HFIP
HFIP
HFIP
HFIP
i-PrOH
1 h
45 min
24 h
2a
3a
4
24 h
5
10 min
10 min
24 h
10 min
45 min
24 h
10 min
10 min
24 h
6
7
8
HSbF6·6H2O
Sc(OTf)3
SbF5
9a
10
11
12
13c
14
15
16
17
AlCl3
ZnCl2
AuCl3
FeCl3
FeCl3
FeCl3
FeCl3
FeCl3
FeCl2
10 min
CF3CH2OH 10 min
CH2Cl2
HFIP
24 h
24 h
41
aPerformed at 50 oC. b37% aq. HCl (w/w) was used. cPerformed at 80 oC.
Scope of trifluoromethylated allenes. Encouraged by the initial results, the scope of triaryl
monotrifluoromethyl allenes was explored (Table 2). The parent 1,1,1-trifluoro-2,4-diphenyl-but-
3-yn-1-ol (1) furnished the corresponding allene 1a with mesitylene as nucleophile in 93% yield.
Replacement of the phenyl ring A with cyclohexyl (1b) or biphenyl (1c) groups lead to a significant
decrease in yield, but with p-tolyl substitution this decrease was less pronounced (1d). However,
o-methyl substitution of ring A (1e) or p-methyl substition of ring B (1f) did not influence the yield
significantly. p-Bromo substitution of phenyl rings A or B slowed down the reaction (1g and 1h),
which could be overcome in most cases by increasing the reaction time (1h). As expected, an
electron-withdrawing (p-fluoro) substituent on phenyl ring B had a deactivating influence (1i).
However, electron-donating (p-methoxy) groups also led to lower yields, due to rapid subsequent
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 6 of 39
1
2
3
4
5
6
7
8
9
indene-forming reactions (1j). The same is true when an electron-donating p-methoxy group is
present on ring A. For example, attempts to isolate allene 1k could only be accomplished in 27%
yield by interrupting the reaction after 5 minutes. In these cases, attempts to isolate the allene by
running at the reaction at lower temperatures or under different concentrations were unsuccessful
since the subsequent cyclization is more facile than the initial allene formation. Finally, the use
of bulkier nucleophiles such as 1,4-diisopropylbenzene also lead to decreased yields (1l-1o) as did
less activated (Cl- and F- substituted) nucleophiles (1p-1r). To confirm the structure of the allenes,
we obtained an X-ray crystal structure of allene 1s.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Table 2. Scope of tetrasubstituted allenes bearing a CF3 group
aHeated at 50 oC. bReaction time was 24 h. cReaction time was 3 h. dReaction time was 1 h.
eReaction time was 5 min. fHeated at 80 oC.
ACS Paragon Plus Environment

Page 7 of 39
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
Scope of trifluoromethylated indenes. In the next step of the study, the scope of indenes was
explored (Table 3). The indenes 2a and 2l were obtained via allenes 1a and 1l in excellent yields.
The indenes 2c, 2d and 2f substituted with phenyl or methyl groups were all obtained in excellent
yields. When a methoxy group is attached in the para position on the phenyl ring B, the yield of
the indene 2j remained high, unlike the case of the para substituted phenyl ring A (2k). The
reaction was slown down when a bromo-substituent was introduced in the phenyl ring B (2n).
1,3,5-Triethylbenzene proved to be a good nucleophile for formation of indenes (entry 2x). By
increasing the temperature to 120 °C, it was possible to use 1,3,5-trimethoxybenzene as a
nucleophile (entry 2y). However, when a chloro-bearing arene was used, the yield dropped
significantly (2s). In the case of indene 2x and 2y, we were unable to isolate the intermediate
allene. Generally, attempts to form indenes from propargylic alcohols using weaker arene
nucleophiles via allenes were unsuccessful (for example, via allenes 1p-1q), due both to the
reduced ability of the nucleophile to capture the propargylic carbocation, as well as the subsequent
deactivating effect of the electron-poor arene on the cyclization of the allene intermediate. Even
under more forcing conditions, propargylic alcohols bearing a bromide or fluoride on ring A or
ring B did not lead to indenes, but instead stopped at the allenes (1g, 1h, 1i, 1o, 1s) previously
described in Table 2.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 8 of 39
1
2
3
4
Table 3. Scope of indenes bearing a CF3 group
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
aReaction time was 24 h. bHeated at 80 oC. cCarried out at 50 oC for 6 h. dReaction time was 1 h.
eIsolated as mixture of regioisomers. fHeated at 120 °C.
Access to 2H-2-trifluoromethyl chromenes. We hypothesized that propargylic alcohols with an
o-hydroxyphenyl moiety should give access to corresponding 2H-2-trifluoromethyl chromenes.
Chromenes (benzopyrans) are a class of organic compounds that exhibit various biological
activities,23 especially their trifluoromethylated derivates.24 Here, we found that the catalytic use
of TfOH gave higher yields than FeCl3. Indeed, when 1,1,1-trifluoro-4-(2-hydroxophenyl)-2-
phenylbut-3-yn-1-ol (3a) was subjected to 10 mol% TfOH/in HFIP,25 we were pleased to observe
formation of chromene 4a in quantitative yield (Table 4). Other nucleophiles such as durene,
ACS Paragon Plus Environment

Page 9 of 39
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
pentamethylbenzene and 1,3,5-trimethoxybenzene proved to be compatible with the reaction
conditions (4b-4d). Slight modifications to the electronic properties of the 2-phenyl ring (4e and
4f) or replacement of the 2-aryl moiety with a 2-alkyl group (4g) were tolerated. Furthermore, the
tert-butyl-dimethylsilyl ether derivatives 3e’ and 3f yielded the same product as their phenolic
precursors (3e), due to an in situ deprotection/cyclization on 1 mmol scale.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Table 4. Scope of chromenes bearing trifluoromethyl group
aPerformed on 1 mmol scale.
Reactivity of secondary α-trifluoromethyl propargylic alcohols in HFIP. In light of the
successful reactions of tertiary CF3-propargylic alcohols, we next tested the reactivity of
secondary CF3-propargylic alcohols in the presence of catalytic TfOH. Unexpectedly, by
applying the same reaction conditions, a bis-arylated alkene 6a was observed (Table 5). An X-ray
crystal structure of the product 6a revealed the Z-geometry of the double bond, as well as a
preferred conformation in which the two mesityl units are aligned. A series of para-substituted
secondary α-trifluoromethyl propargylic alcohols was tested for Friedel-Crafts reactions with
methyl- and methoxy-substituted benzenes as nucleophiles (Table 5). Methyl- (5b) and methoxy-
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 10 of 39
1
2
3
4
5
6
7
8
9
(5c) substituted propargyl alcohols furnished products 6b and 6c in slightly higher yields than the
parent alcohol 6a. Substitution with a cyano-group led to significant loss in reactivity (6d). In
addition to the electronic deactivating effect of the CN group, the lowered yield may also
potentially be due to the ability of this mildly basic group to buffer the Brønsted acid catalyst. The
less electron-withdrawing bromine substituent led only to a minor drop in yield (6e). When 1,3,5-
trimethoxybenzene was used as nucleophile, substantially lower yield of 6f was obtained with the
parent alcohol 5a. However, methoxy-substituted alcohol 5c furnished the corresponding product
6g in good yield. With other methyl-substituted benzenes, such as p-xylene (6h),
pentamethylbenzene (6i-j) and durene (6k), as nucleophiles, reaction products were also obtained
in good to excellent yields.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Table 5. Bis-addition to secondary α-trifluoromethyl propargylic alcoholsa
OH
TfOH (10 mol%)
Ar
CF3
CF3
Ar
HFIP, 50 °C, 16 h
H
R
R
H
Ar
(3 equiv)
5d, R = CN
6a-6j
5a, R = H
5b, R = Me
5c, R = OMe
5e, R = Br
Ar1 Ar1
CF3
Mes
Mes
CF3
Mes
Mes
CF3
R
MeO
R = 6b, Me, 77% (92%b)
6c, OMe, 81%
6a, 75%
6f, 73%
6d, CN, 22%c
6e, Br, 61%
Ar2 Ar2
Ar3 Ar3
CF3
CF3
CF3
R
MeO
6g, 49%
6h, R = H, 95%
6i, R = Me, 88%
6j, 65%
OMe
Ar1
=
Ar3
=
Ar2
=
MeO
OMe
Ar
Ar
CF3
6a
R
aIsolated yields after column chromatography. bPerformed at 1 mmol scale.
cReaction heated at 100 oC for 88 h. Mes = mesityl.
ACS Paragon Plus Environment

Page 11 of 39
The Journal of Organic Chemistry
1
2
3
4
5
6
Mechanistic experiments. To determine whether the FeCl3 acts as a Lewis acid or Brønsted acid
catalyst,7 reactions were carried out in the presence of catalytic quantities (10 mol%) of the
hindered Brønsted base 2,6-di-tert-butylpyridine, which does not coordinate most metal ions,26
7
8
9
and
in
the
presence
of
a
similar
amount
of
Proton-sponge
(1,8-
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Bis(dimethylamino)naphthalene, N,N,N′,N′-Tetramethyl-1,8-naphthalenediamine). In both cases,
no reaction was observed, suggesting that the role of the FeCl3 is to generate a hidden Brønsted
acid catalyst. However, substituting FeCl3 with 10 mol% HCl gave only traces of product,
excluding HCl as the active catalyst. Therefore, we suspect that the active catalytic species is a
partially hydrated or HFIP-bound ferric ion that acts as a Brønsted acid catalyst, although rapid
and complex equilibria between many possible species make this very difficult to determine
definitively.
Insight into the mechanism of the cyclization of allenes to indenes can be extracted from
the observed scope of substrates (Table 3). When a methyl group is in the ortho position on the
phenyl ring A, like in the cases of 1e and 1m, the formation of the indene is disabled. Para-bromo
substitution in phenyl ring A of the starting alcohols also leads to significantly lower cyclization
rates of 1g and 1o. To distinguish whether ring A or ring B are involved in the indene-forming
cyclization event, deuterated substrate 1-d5 was exposed to the standard reaction conditions.
1
2
Analysis of the H and H NMR and high resolution MS of the resulting product revealed its
structure to be that of 2a-d4 as shown in Scheme 3, consistent with a Nazarov-type cyclization
involving ring A rather than one involving ring B (Scheme 4). Similar cyclizations have been
reported to be catalyzed by Yb(OTf)3,27 AgOTf, and TfOH.28
Scheme 3. Reaction of pentadeuterated substrate 1-d5 with mesitylene
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 12 of 39
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Scheme 4. Proposed mechanism of indene formation
Regarding the bis-addition of arenes to secondary propargylic alcohols (Table 5), the proposed
mechanism is shown in Scheme 5. First, the hydroxyl group is activated by the TfOH/HFIP
hydrogen-bond network, which is followed by nucleophilic substitution at the γ-carbon. Then, the
C-C double bond that is more distant from the CF3 group is protonated, forming a carbocation that
is both benzylic and allylic. This carbocation is attacked by a second arene molecule, furnishing a
tri-substituted allylic trifluoromethane.
Scheme 5. Plausible mechanism for bis-addition to secondary α-CF3 propargylic alcohols
CONCLUSION
We have described a straightforward catalytic method to access triaryl CF3- bearing allenes,
indenes, chromenes and 1,1,1-trifluoro-3-butenes directly from α-CF3 propargylic alcohols. The
important role of HFIP solvent in combination with strong Brønsted or Lewis acids such as triflic
acid or FeCl3 were key to the observed reactivity. Mechanistic experiments suggest the initial
ACS Paragon Plus Environment

Page 13 of 39
The Journal of Organic Chemistry
1
2
3
4
5
6
formation of a CF3-allene intermediate, which subsequently cyclizes to the corresponding CF3-
indene.
7
8
9
EXPERIMENTAL SECTION
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
General Information. All Friedel-Crafts reactions were performed in 10 mL glass pressure tubes
under an atmosphere of air. Elevated temperatures were achieved by way of a stirrer-hotplate,
metal heating block and thermocouple. Purification of reaction products was carried out by flash
column chromatography using Merck silica gel (40-63 μm). Analytical thin layer chromatography
(TLC) was performed on aluminum sheets precoated with silica gel 60 F254 (Merck), cut to size.
1
Visualization was accomplished with UV light. H NMR spectra were recorded on a Bruker
UltraShield Plus 400 (400 MHz) spectrometer at ambient temperature and are reported in ppm
using solvent as internal standard (residual CHCl3 at 7.26 ppm). 13C{1H} NMR spectra were
recorded on a Bruker UltraShield Plus 400 (100 MHz) spectrometer at ambient temperature and
19
are reported in ppm using solvent as internal standard (CDCl3 at 77.16 ppm). F NMR spectra
were recorded on a Bruker UltraShield Plus 400 (376.5 MHz) spectrometer at ambient temperature
and are reported in ppm using trifluoroacetic acid as external standard (peak at –76.55 ppm). Data
are reported as: multiplicity (ap = apparent, br = broad, s = singlet, d = doublet, t = triplet, q =
quartet, quint = quintet, sext = sextet, m = multiplet, dd = doublet of doublets, ddd = doublet of
doublet of doublets, dddd = doublet of doublet of doublet of doublets, qd = quartet of doublets, dt
= doublet of triplets, dm = doublet of multiplets, td = triplet of doublets, quintd = quintet of
doublets), coupling constants (in Hz) and integration. In cases where compounds were isolated as
mixtures of regioisomers, signals corresponding to protons of the major regioisomer were
integrated as integer values matching the number of protons in the molecule. Non-integer
integration values correspond to signals of protons of minor regioisomers or to overlapping signals
of regioisomers. GC/MS analysis was conducted on a GC System 7820A (G4320) connected to a
MSD block 5977E (G7036A) using Agilent High Resolution Gas Chromatography Column HP-
5MS UI, 30 m×0.250 mm×0.25 µm. High resolution mass spectrometry (HRMS) analysis was
performed on instruments GCT 1er Waters (EI and CI), MicroTOF-Q Bruker (ESI), and a GC
Thermo Scientific Trace 1300 GC unit coupled to an APPI MasCom source mounted on a Thermo
Scientific Exactive Plus EMR mass unit (Orbitrap FT-HRMS analyzer). Materials: All
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 14 of 39
1
2
3
4
5
6
commercial materials were purchased from Sigma-Aldrich, Alfa Aesar and FluoroChem, and were
used as received, without further purification.
7
8
9
Preparation of tertiary propargylic alcohols
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
General procedure A for tertiary propargylic alcohols synthesis: Trifluoromethyl phenyl
ketone (5.0-10 mmol, 1.0 equiv) and phenyl acetylene (1.5 equiv) were diluted in 10-15 mL
DMSO. CuI (0.10 equiv) and K2CO3 (0.20 equiv) were added and the reaction mixture was heated
at 50-70 C for 24 h. The reaction mixture was then treated with brine, extracted with CH2Cl2,
dried with anhydrous sodium sulfate and concentrated at reduced pressure. The product was then
purified by silica gel column chromatography.
o
HO CF3
1,1,1-Trifluoro-2,4-diphenylbut-3-yn-2-ol was prepared according to general
procedure A and isolated as a yellow oil. Spectral data are in agreement with the
1
literature.29 Isolated 2.55 g, 85% yield. H NMR (400 MHz, CDCl3): δ (ppm)
7.86–7.79 (m, 2H), 7.57–7.52 (m, 2H), 7.48–7.42 (m, 3H), 7.42–7.32 (m, 3H),
3.10 (s, 1H).
HO CF3
4-Cyclohexyl-1,1,1-trifluoro-2-phenylbut-3yn-2-ol was prepared according to
general procedure A and isolated as a yellow oil. Spectral data are in agreement
with the literature.30 Isolated 1.32 g, 44% yield. 1H NMR (400 MHz, CDCl3): δ
(ppm) 7.82-7.68 (m, 2H), 7.43-7.39 (m, 3H), 2.92 (s, 1H), 2.54 (sept. J = 4 Hz,
1H), 1.90-1.29 (m, 10H).
HO CF3
1,1,1-Trifluoro-2-phenyl-4-(p-toluyl)but-3-yn-2-ol was prepared according
to general procedure A and isolated as a pale yellow oil. Spectral data are in
agreement with the literature.31 Isolated 2.55 g, 85% yield. H NMR (400
MHz, CDCl3): δ (ppm) 7.86-7.78 (m, 2H), 7.52–7.36 (m, 5H), 7.17 (d, J =
1
Me
7.8 Hz, 2H), 3.08 (s, 1H), 2.38 (s, 3H).
HO CF3
1,1,1-Trifluoro-4-phenyl-2-(p-toluyl)but-3-yn-2-ol was prepared according
to general procedure A and isolated as a yellow oil. Spectral data are in
Me
1
agreement with the literature.32 Isolated 0.93 g, 31% yield. H NMR (400
MHz, CDCl3): δ (ppm) 7.62 (d, J = 8.1 Hz, 2H), 7.48–7.43 (m, 2H), 7.35–
7.25 (m, 3H), 7.16 (d, J = 8.7 Hz, 2H), 2.98 (s, 1H), 2.31 (s, 3H).
HO CF3
4-((1,1'-Biphenyl)-4-yl)-1,1,1-trifluoro-2-phenylbut-3-yn-2-ol
was
prepared according to general procedure A and isolated as yellow solid.
1
Isolated 2.01 g, 67% yield. H NMR (500 MHz, CDCl3):  (ppm) 7.86-
7.80 (m, 2H), 7.63-7.57 (m, 6H), 7.48-7.42 (m, 4H), 7.38 (t, J = 7.4 Hz,
2H), 3.09 (s, 1H). 13C{1H} NMR (100 MHz, CDCl3): δ (ppm) 142.5,
ACS Paragon Plus Environment

Page 15 of 39
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
140.2, 135.4, 132.7, 129.7, 129.1, 128.4, 128.1, 127.4, 127.3, 127.2, 123.5 (q, J = 283.9 Hz), 119.9,
88.1, 85.1, 73.5 (q, J = 32.3 Hz), 19F NMR (376.5 MHz, CDCl3, CF3COOH - ext. st.):  (ppm) –
80.9 (s, 3F). HRMS (APPI+-Orbitrap) m/z: [M+H–H2O]+: Calcd for C22H15F3O 335.1042; Found
335.1054 (3.5 ppm).
9
4-(4-Bromophenyl)-1,1,1-trifluoro-2-phenylbut-3-yn-2-ol was prepared
HO CF3
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
according to general procedure A and isolated as a yellow oil. Spectral data
are in agreement with the literature.13 Isolated 2.70 g, 90% yield. Rf = 0.43
Br
(petroleum ether/EtOAc 9:1). 1H NMR (500 MHz, CDCl3):  (ppm) 7.68 (d,
J = 8.6 Hz, 2H), 7.58-7.50 (m, 4H), 7.44-7.35 (m, 3H), 3.26 (s, 1H).
4-(4-Bromophenyl)-1,1,1-trifluoro-2-phenylbut-3-yn-2-ol was prepared
HO CF3
according to general procedure A and isolated as a yellow oil. Spectral data
are in agreement with the literature.13 Isolated 1.56 g, 52% yield. Rf = 0.44
Br
1
(petroleum ether/EtOAc 9:1). H NMR (400 MHz, CDCl3):  (ppm) 7.75-
7.69 (m, 2H), 7.46-7.41 (m, 2H), 7.39-7.34 (m, 3H), 7.34-7.28 (m, 2H), 3.09 (s, 1H).
HO CF3
1,1,1-Trifluoro-2-(4-methoxyphenyl)-4-phenylbut-3-yn-2-ol was prepared
according to general procedure A and isolated as pale yellow solid. Spectral
1
data are in agreement with the literature.30 Isolated 1.92 g, 64% yield. H
OMe
NMR (400 MHz, CDCl3):  (ppm) 7.73 (d, J = 8.8 Hz, 2H), 7.57-7.50 (m,
2H), 7.43–7.32 (m, 3H), 6.96 (d, J = 8.9 Hz, 2H), 3.84 (s, 3H), 3.10 (s, 1H).
1,1,1-Trifluoro-2-(4-methoxy-phenyl)-4-phenylbut-3-yn-2-ol was prepared
HO CF3
according to general procedure A and isolated as a yellow oil. Spectral data
are in agreement with the literature.30 Isolated 2.73 g, 91% yield. Rf = 0.36
MeO
1
(petroleum ether/EtOAc 9:1). H NMR (400 MHz, CDCl3):  (ppm) 7.73
(dt, J = 8.8 Hz, 3.0 Hz, 2H), 7.56-7.51 (m, 2H), 7.45-7.33 (m, 3H), 6.93-6.10 (m, 2H), 3.84 (s,
3H), 3.10 (s, 1H).
HO CF3
1,1,1-Trifluoro-2-(4-fluorophenyl)-4-phenylbut-3-yn-2-ol was prepared
according to general procedure A and isolated as a yellow oil. Spectral data
F
are in agreement with the literature.13 Isolated 2.85 g, 95% yield. Rf = 0.40
(petroleum ether/EtOAc 9:1). 1H NMR (400 MHz, CDCl3):  (ppm) 7.83-7.76
(m, 2H), 7.56-7.50 (m, 2H), 7.45-7.34 (m, 3H), 7.16-7.08 (m, 2H), 3.29 (s, 1H).
Preparation of allenes
General procedure B: To a 10 mL reaction tube was added the catalyst (10 mol%), HFIP
(0.50 M relative to propargylic alcohol), propargylic alcohol (0.17-0.40 mmol, 1.0 equiv),
followed by the arene nucleophile (5.0 equiv). The mixture was allowed to stir at 25 °C until judged
complete by TLC (9:1 Petroleum ether:EtOAc), typically after 10 min. The reactions typically turn
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 16 of 39
1
2
3
4
5
an opaque black. The crude reaction mixture was directly transferred for silica gel
chromatography.
General procedure C: To a 10 mL reaction tube was added the catalyst (10 mol%), HFIP
(0.5-1.0 M relative to propargylic alcohol), and propargylic alcohol (0.17-0.40 mmol, 1.0 equiv),
followed by the arene nucleophile (5.0 equiv). The reactions typically turn an opaque black. After
completion of the reaction as judged by TLC, the crude reaction mixture was directly transferred
for silica gel chromatography.
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Characterization data for allenes
1-Mesityl-1,3-diphenyl-4,4,4-trifluoro-1,2-butadiene (1a) was prepared according to
general procedure B from 1,1,1-trifluoro-2,4-diphenylbut-3-yn-2-ol (100 mg, 0.363
CF3
mmol) and mesitylene (253 µL, 1.82 mmol, 5.0 equiv) with 5.9 mg (0.036 mmol) of
FeCl3 in 0.73 mL of HFIP. The reaction mixture was stirred at ambient temperature
for 10 min. Purification by flash column chromatography over silica (petroleum ether) gave 128
1
mg (93% yield) of white solid. Rf = 0.83 (petroleum ether/EtOAc 9:1). H NMR (400 MHz,
CDCl3): δ (ppm) 7.49 (d, J = 7.5 Hz, 2H), 7.43–7.12 (m, 8H), 6.94 (s, 2H), 2.32 (s, 3H), 2.17 (s,
6H). 13C{1H} NMR (100 MHz, CDCl3): δ (ppm) 205.1 (q, J = 3.5 Hz), 138.1, 137.1, 133.3, 130.2,
129.9, 129.2, 128.9, 128.7, 128.6, 128.5, 127.6, 126.7, 123.7 (q, J = 275.1 Hz), 114.1, 104.0 (q, J
= 34.3 Hz), 21.2, 20.4. 19F NMR (376.5 MHz, CDCl3, CF3COOH - ext. st.):  (ppm) –62.5 (s, 3F).
HRMS (APPI+-Orbitrap) m/z: [M]+. Calcd for C25H21F3 378.1590; Found 378.1596 (1.5 ppm).
1-Cyclohexyl-1-mesityl-3-phenyl-4,4,4-trifluoro-1,2-butadiene (1b) was prepared
according to general procedure B from 4-cyclohexyl-1,1,1-trifluoro-2-phenylbut-3yn-
CF3
2-ol (49 mg, 0.17 mmol) and mesitylene (70 µL, 0.50 mmol, 3.0 equiv) with 2.7 mg
(0.017 mmol) of FeCl3, in 0.33 mL of HFIP. The reaction mixture was stirred at 50
oC for 24 h. Purification by flash column chromatography over silica (petroleum ether) gave 33
1
mg (51% yield) of the product. H NMR (400 MHz, CDCl3): δ (ppm) 7.48 (d, J = 7.8 Hz, 2H),
7.37 (t, J = 7.7 Hz, 2H), 7.30 (t, J = 7.2 Hz, 1H), 6.89 (s, 2H), 2.41-2.15 (m, 10H), 2.03-1.91 (m,
2H), 1.87-1.75 (m, 2H), 1.75-1.66 (m, 1H), 1.43-1.18 (m, 5H). 13C{1H} NMR (100 MHz, CDCl3):
δ (ppm) 201.5 (q, J = 4.0 Hz), 137.2, 131.9, 130.9, 128.7, 128.0, 127.32, 127.31, 124.1 (q, J =
272.7 Hz), 118.1, 102.2 (q, J = 33.8 Hz), 43.4, 32.1, 31.9, 26.7, 26.7, 26.2, 21.1. 19F NMR (376.5
MHz, CDCl3):  (ppm) –58.1 (s, 3F). HRMS (APPI+-Orbitrap) m/z: [M]+. Calcd for C25H27F3
384.2059; Found 384.2059 (–0.1 ppm).
1-Mesityl-1-(1,1'-biphenyl-4-yl)-4,4,4-trifluoro-3-phenyl-1,2-butadiene (1c) was
prepared according to general procedure B from 4-((1,1'-biphenyl)-4-yl)-1,1,1-
CF3
trifluoro-2-phenylbut-3-yn-2-ol (59 mg, 0.17 mmol) and mesitylene (71 µL, 0.51
mmol, 3.0 equiv) with 2.7 mg (0.017 mmol) of FeCl3, in 0.34 mL of HFIP. The
reaction mixture was stirred at ambient temperature for 10 min. Purification by
flash column chromatography over silica (petroleum ether) gave 31 mg (40% yield)
of the product with 95% purity (the rest is the corresponding indene that started to form quickly).
1H NMR (400 MHz, CDCl3): δ (ppm) 7.67-7.56 (m, 4H), 7.54 (d, J = 7.5 Hz, 2H), 7.46 (t, J = 7.5
ACS Paragon Plus Environment

Page 17 of 39
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
Hz, 2H), 7.43-7.30 (m, 6H), 6.99 (s, 2H), 2.36 (s, 3H), 2.23 (s, 6H). 13C{1H} NMR (100 MHz,
CDCl3): δ (ppm) 205.3 (q, J = 3.9 Hz), 141.5, 140.6, 138.1, 137.2, 132.2, 130.2, 129.9, 129.0,
128.9, 128.8, 128.6, 127.9, 127.7, 127.7, 127.2, 127.1, 123.7 (q, J = 273.3 Hz), 113.9, 104.1 (q, J
19
= 34.1 Hz), 21.2, 20.4. F NMR (376.5 MHz, CDCl3):  (ppm) –58.1 (s, 3F). HRMS (APPI+-
Orbitrap) m/z: [M]+. Calcd for C31H25F3 454.1903; Found 454.1903 (0.1 ppm).
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
1-Mesityl-4,4,4-trifluoro-1-(p-toluyl)-3-phenyl-1,2-butadiene (1d) was prepared
according to general procedure B from 1,1,1-trifluoro-2-phenyl-4-(p-tolulyl)but-3-
CF3
yn-2-ol (85 mg, 0.29 mmol) and mesitylene (117 µL, 0.84 mmol, 5.0 equiv) with 4.6
mg (0.028 mmol) of FeCl3, in 0.57 mL of HFIP. The reaction mixture was stirred at
ambient temperature for 10 min. Purification by flash column chromatography over
1
silica (petroleum ether) gave 84 mg (74% yield) of the product. H NMR (400 MHz, CDCl3): δ
(ppm) 7.63 (d, J = 7.6 Hz, 2H), 7.50-7.31 (m, 3H), 7.33-7.22 (m, 4H), 7.07 (s, 2H), 2.46 (s, 3H),
2.44 (s, 3H), 2.32 (6H). 13C{1H} NMR (100 MHz, CDCl3): δ (ppm) 205.0 (q, J = 4.0 Hz), 138.7,
138.0, 137.1, 130.4, 130.3, 130.0, 128.9, 128.7, 128.5, 127.6, 127.1, 126.1, 123.8 (q, J = 273.5
Hz), 114.1, 103.9 (q, J = 34.2 Hz), 21.4, 21.2, 20.4. 19F NMR (376.5 MHz, CDCl3):  (ppm) –59.2
(s, 3F). HRMS (APPI+-Orbitrap) m/z: [M]+. Calcd for C26H23F3 392.1746; Found 392.1750 (1.0
ppm).
1-Mesityl-3-phenyl-3-(2-toluyl)-4,4,4-trifluoro-1,2-butadiene (1e) was prepared
according to general procedure B from 1,1,1-trifluoro-4-phenyl-2-(o-tolulyl)but-3-
CF3
yn-2-ol (91 mg, 0.31 mmol) and mesitylene (188 µL, 1.57 mmol, 5.0 equiv) with 5.1
mg (0.031 mmol) of FeCl3, in 0.63 mL of HFIP. The reaction mixture was stirred at
ambient temperature for 10 min. Purification by flash column chromatography over silica
(petroleum ether) gave 118 mg (96% yield) of white solid. Rf = 0.87 (petroleum ether/EtOAc 9:1).
1H NMR (400 MHz, CDCl3): δ (ppm) 7.52 (d, J = 7.6 Hz, 2H), 7.46–7.33 (m, 3H), 7.33–7.23 (m,
2H), 7.16 (t, J = 7.6 Hz, 1H), 7.00 (s, 2H), 6.91 (d, J = 7.8 Hz, 1H), 2.54 (s, 3H), 2.39 (s, 3H), 2.24
(s, 6H). 13C{1H} NMR (100 MHz, CDCl3): δ (ppm) 205.4 (q, J = 4.3 Hz), 137.8, 137.6, 136.9,
132.6, 132.3, 131.7, 130.7, 128.9, 128.8, 128.4, 128.3, 128.2, 128.0, 126.5, 123.8 (q, J = 274.6
Hz), 112.5, 101.5 (q, J = 34.5 Hz), 22.0, 21.2, 20.4. 19F NMR (376.5 MHz, CDCl3, CF3COOH-
ext. st.):  (ppm) –58.2 (s, 3F). HRMS (APPI+-Orbitrap) m/z: [M]+. Calcd for C26H23F3 392.1746;
Found 392.1747 (0.2 ppm).
1-Mesityl-1-phenyl-3-toluyl-4,4,4-trifluoro-1,2-butadiene (1f) was prepared
according to general procedure B from 1,1,1-trifluoro-4-phenyl-2-(p-tolulyl)but-3-
yn-2-ol (100 mg, 0.346 mmol) and mesitylene (241 µL, 1.73 mmol, 5.0 equiv) with
3.5 mg (0.022 mmol) of FeCl3, in 0.69 mL of HFIP. The reaction mixture was stirred
CF3
at ambient temperature for 10 min. Purification by flash column chromatography over silica
(petroleum ether) gave 122 mg (93% yield) of a colorless oil. Rf = 0.93 (petroleum ether/EtOAc
9:1). 1H NMR (400 MHz, CDCl3): δ (ppm) 7.43 (d, J = 8.0 Hz, 2H), 7.40–7.32 (m, 3H), 7.32–7.27
(m, 2H), 7.21 (d, J = 8.0, 2H), 7.00 (s, 2H), 2.39 (s, 3H), 2.37 (s, 3H), 2.23 (s, 6H). 13C{1H} NMR
(100 MHz, CDCl3): δ (ppm) 204.8 (q, J = 3.8 Hz), 138.5, 138.0, 137.1, 133.4, 129.6, 129.1, 128.7,
128.5, 127.5, 127.1, 127.1, 126.7, 123.8 (q, J = 275.2 Hz), 113.9, 103.8 (q, J = 34.3 Hz), 21.3,
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 18 of 39
1
2
3
4
5
19
21.2, 20.4. F NMR (376.5 MHz, CDCl3, CF3COOH-ext. st.):  (ppm) –58.3 (s, 3F). HRMS
(APPI+-Orbitrap) m/z: [M]+. Calcd for C26H23F3 392.1746; Found 392.1744 (–0.6 ppm).
6
7
8
9
1-(4-Bromophenyl)-1-mesityl-3-phenyl-4,4,4-trifluoro-1,2-butadiene (1g) was
prepared according to general procedure B from 4-(p-bromophenyl)-1,1,1-trifluoro-
2-phenyl-but-3-yn-2-ol (86 mg, 0.24 mmol) and mesitylene (146 µL, 1.05 mmol, 5.0
equiv) with 3.4 mg (0.021 mmol) of FeCl3, in 0.5 mL of HFIP. The reaction mixture
was stirred at ambient temperature for 10 min. Purification by flash column
CF3
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Br
chromatography over silica (petroleum ether) gave 78 mg (70% yield) of a colorless oil. 1H NMR
(400 MHz, CDCl3):  (ppm) 7.52-7.41 (m, 4H), 7.41-7.29 (m, 3H), 7.10 (d, J = 8.6 Hz, 2H), 6.95
(s, 2H), 2.32 (s, 3H), 2.15 (s, 6H). 13C{1H} NMR (100 MHz, CDCl3):  (ppm) 204.9 (q, J = 3.8
Hz), 138.3, 137.0, 132.3, 129.8, 129.3, 128.9, 128.8, 128.7, 128.1, 127.6, 127.6, 123.5 (q, J = 273.5
Hz), 122.7, 113.3, 104.3 (q, J = 34.3 Hz), 21.1, 20.3. 19F NMR (376.5 MHz, CDCl3, C6F6-ext. st.):
 (ppm) –62.5 (s, 3F). HRMS (APPI+-Orbitrap) m/z: [M]+. Calcd for C25H2079BrF3 456.0695;
Found 456.0700 (1.1 ppm).
3-(4-Bromophenyl)-1-mesityl-1,3-diphenyl-4,4,4-trifluoro-1,2-butadiene (1h) was
CF3
prepared according to general procedure B from 4-(4-bromophenyl)-1,1,1-trifluoro-
2,4-diphenylbut-3-yn-2-ol (100 mg, 0.286 mmol) and mesitylene (199 µL, 1.43
mmol, 5.0 equiv) with 4.3 mg (0.029 mmol) of FeCl3, in 0.57 mL of HFIP. The
reaction mixture was stirred at ambient temperature for 10 min. Purification by flash
Br
column chromatography over silica (petroleum ether) gave 118 mg (90% yield) of a colorless oil.
Rf = 0.82 (petroleum ether/EtOAc 9:1). 1H NMR (400 MHz, CDCl3): δ (ppm) 7.49 (d, J = 8.6 Hz,
2H), 7.38–7.28 (m, 5H), 7.25–7.18 (m, 2H), 6.95 (s, 2H), 2.33 (s, 3H), 2.16 (s, 6H). 13C{1H} NMR
(100 MHz, CDCl3): δ (ppm) 205.0 (q, J = 3.8 Hz), 138.2, 137.0, 132.9, 132.1, 129.6, 129.3, 129.2,
129.2, 128.8, 127.1, 126.7, 123.5 (q, J = 275.0 Hz), 122.7, 114.6, 103.2 (q, J = 34.6 Hz), 21.2,
20.4. 19F NMR (376.5 MHz, CDCl3, C6F6-ext. st.):  (ppm) –62.5 (s, 3F). HRMS (APPI+-Orbitrap)
m/z: [M]+. Calcd for C25H2079BrF3 456.0695; Found 456.0699 (0.9 ppm).
3-(4-Fluorophenyl)-1-mesityl-1-phenyl-4,4,4-trifluoro-1,2-butadiene
(1i)
was
prepared according to modified general procedure B from 1,1,1-trifluoro-2-(p-
fluorophenyl)-4-phenyl-but-3-yn-2-ol (72 mg, 0.21 mmol) and mesitylene (146 µL,
1.05 mmol, 5.0 equiv) with 3.4 mg (0.021 mmol) of FeCl3, in 0.42 mL of HFIP. The
reaction mixture was stirred at ambient temperature for 1 h. Purification by flash
CF3
F
column chromatography over silica (petroleum ether) gave 50 mg (52% yield) of white solid. 1H
NMR (400 MHz, CDCl3):  (ppm) 7.56-7.48 (m, 2H), 7.44-7.33 (m, 3H), 7.33-7.27 (m, 2H), 7.16-
7.07 (m, 2H), 7.02 (s, 2H), 2.39 (s, 3H), 2.23 (s, 6H). 13C{1H} NMR (100 MHz, CDCl3):  (ppm)
204.8 (q, J = 3.6 Hz), 162.9 (d, J = 246.9 Hz), 138.2, 137.0, 133.1, 129.7, 129.5 (d, J = 8.1 Hz),
129.2, 128.8, 128.7, 126.6, 126.2 (d, J = 3.3 Hz), 123.6 (q, J = 273.3 Hz), 116.1 (d, J = 21.7 Hz),
114.3, 103.1 (q, J = 34.6 Hz), 21.3, 20.3. 19F NMR (376.5 MHz, CDCl3, C6F6-ext. st.):  (ppm) –
62.8 (s, 3F), –116.0 (m, 1F). HRMS (APPI+-Orbitrap) m/z: [M]+. Calcd for C25H20F4 396.1496;
Found 396.1500 (1.0 ppm).
ACS Paragon Plus Environment

Page 19 of 39
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
1-Mesityl-3-(4-methoxyphenyl)-1-phenyl-trifluoro-1,2-butadiene
(1j)
was
prepared according to modified general procedure B from 1,1,1-trifluoro-2-(4-
metoxyphenyl)-4-phenylbut-3-yn-2-ol ol (71 mg, 0.25 mmol) and mesitylene (102
µL, 0.735 mmol, 3.0 equiv) with 4.0 mg (0.025 mmol) of FeCl3, in 0.98 mL of
HFIP. The reaction mixture was stirred at ambient temperature for 10 min.
CF3
OMe
Purification by flash column chromatography over silica (petroleum ether/EtOAc 40:1 to 30:1)
gave 79 mg (82% yield) of colorless oil. Rf = 0.81 (petroleum ether/EtOAc 9:1). H NMR (500
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
1
MHz, CDCl3): δ (ppm) 7.42 (d, J = 8.5 Hz, 2H), 7.38–7.21 (m, 5H), 6.96 (s, 2H), 6.90 (d, J = 8.8
Hz, 2H), 3.82 (s, 3H), 2.34 (s, 3H), 2.18 (s, 6H). 13C{1H} NMR (125 MHz, CDCl3): δ (ppm) 204.5
(q, J = 3.5 Hz), 159.8, 138.0, 137.1, 133.5, 130.1, 129.1, 128.9, 128.7, 128.5, 126.6, 123.8 (q, J =
275.0 Hz), 122.2, 114.3, 113.8, 103.6 (q, J = 34.5 Hz), 55.4, 21.2, 20.4. 19F NMR (376.5 MHz,
CDCl3, CF3COOH-ext. st.):  (ppm) –59.1 (s, 3F). HRMS (APPI+-Orbitrap): m/z [M]+. Calcd for
C26H23F3O 408.1696; Found 408.1708 (2.9 ppm).
1-Mesityl-4-(4-methoxyphenyl)-3-phenyl-4,4,4-trifluoro-1,2-butadiene (1k) was
prepared according to modified general procedure B from 1,1,1-trifluoro-4-(4-
CF3
metoxyphenyl)-2-phenylbut-3-yn-2-ol ol (73 mg, 0.24 mmol) and mesitylene (84
µL, 0.74 mmol, 2.5 equiv) with 3.9 mg (0.024 mmol) of FeCl3, in 0.48 mL of HFIP.
The reaction mixture was stirred at ambient temperature for 10 min. Purification
MeO
by flash column chromatography over silica gave 26 mg (27% yield) of the product. 1H NMR (400
MHz, CDCl3):  (ppm) 7.50 (d, J = 7.6 Hz, 2H), 7.41-7.29 (m, 3H), 7.20 (d, J = 8.8 Hz, 2H), 6.95
(s, 2H), 6.88 (d, J = 8.8 Hz, 2H), 3.82 (s, 3H), 2.33 (s, 3H), 2.19 (s, 6H). 13C{1H} NMR (100 MHz,
CDCl3):  (ppm) 204.8 (q, J = 3.9 Hz), 160.0, 137.9, 137.1, 130.5, 130.1, 128.8, 128.7, 128.4,
128.0, 127.6, 127.6, 125.3, 123.7 (q, J = 273.3 Hz), 114.6, 113.7, 103.8 (q, J = 34.1 Hz), 55.5,
21.2, 20.3. 19F NMR (376.5 MHz, CDCl3):  (ppm) –59.3 (s, 3F). HRMS (APPI+-Orbitrap) m/z:
[M+H]+. calculated for C26H24F3O 409.1774; found 409.1768 (–1.5 ppm).
1-(2,5-Diisopropylphenyl)-1,3-diphenyl-4,4,4-trifluoro-1,2-butadiene (1l) was
prepared according to general procedure B from 1,1,1-trifluoro-2,4-diphenylbut-3-
CF3
yn-2-ol (104 mg, 0.376 mmol) and diizopropyl benzene (356 µL, 1.88 mmol, 5.0
equiv) with 6.1 mg (0.038 mmol) of FeCl3, in 0.75 mL of HFIP. The reaction
mixture was stirred at ambient temperature for 10 min. Purification by flash column
chromatography over silica (petroleum ether) gave 103 mg (65% yield) of a colorless oil. Rf = 0.82
(petroleum ether/EtOAc 9:1). 1H NMR (400 MHz, CDCl3): δ (ppm) 7.45 (d, J = 7.9 Hz, 2H), 7.35–
7.27 (m, 2H), 7.25–7.14 (m, 8H), 7.20–7.12 (m, 1H), 2.94 (sept, J = 6.8 Hz, 1H), 2.83 (sept, J =
6.9 Hz, 1H), 1.18 (d, J = 6.9 Hz, 6H), 1.04 (d, J = 6.8 Hz, 3H), 0.94 (d, J = 6.9 Hz, 3H). 13C{1H}
NMR (125 MHz, CDCl3):  (ppm) 205.5 (q, J = 3.6 Hz), 146.7, 145.0, 134.7, 132.0, 130.1, 128.9,
128.9, 128.5, 128.5, 128.3, 127.3, 127.3, 127.2, 126.2, 123.6 (q, J = 273.6 Hz), 116.4, 103.9 (q, J
= 34.1 Hz), 33.7, 30.4, 24.4, 24.1, 24.1, 24.1. 19F NMR (376.5 MHz, CDCl3, CF3COOH-ext. st.):
 (ppm) –58.7 (s, 3F). HRMS (APPI+-Orbitrap) m/z [M]+. Calcd for C28H27F3 420.2059; Found
420.2062 (0.7 ppm).
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 20 of 39
1
2
3
4
5
6
7
8
1-(2,5-Diisopropylphenyl)-3-phenyl-3-(2-toluyl)-4,4,4-trifluoro-1,2-butadiene
(1m) was prepared according to modified general procedure B from 1,1,1-trifluoro-
4-phenyl-2-(o-tolulyl)but-3-yn-2-ol (63 mg, 0.22 mmol) and diisopropylbenzene
(123 µL, 0.647 mmol, 3.0 equiv) with 3.5 mg (0.022 mmol) of FeCl3, in 0.86 mL
CF3
of HFIP. The reaction mixture was stirred at ambient temperature for 3 h. Purification by flash
column chromatography over silica (petroleum ether) gave 63 mg (58% yield) of colorless oil. Rf
= 0.84 (petroleum ether/EtOAc 9:1). 1H NMR (500 MHz, CDCl3): δ (ppm) 7.49 (d, J = 7.7 Hz, 2H),
7.41–7.34 (m, 2H), 7.34–7.28 (m, 2H), 7.23 (d, J = 2.0 Hz, 1H), 7.21 (d, J = 4.0 Hz, 2H) 7.18–
7.13 (m, 1H), 7.11 (d, J = 1.7 Hz, 1H), 7.03 (d, J = 7.6 Hz, 1H), 3.00 (sept, J = 6.8 Hz, 1H), 2.87
(sept, J = 6.9 Hz, 1H) 2.30 (s, 3H), 1.30–1.16 (d, J = 7.0 Hz, 6H), 1.04 (d, J = 6.9 Hz, 3H), 1.02
(d, J = 6.9 Hz, 3H). 13C{1H} NMR (125 MHz, CDCl3): δ (ppm) 205.7 (q, J = 3.6 Hz), 146.6, 144.8,
137.0, 134.7, 134.0, 131.3, 130.6, 129.7, 128.8, 128.3, 128.3, 128.2, 127.4 (q, J = 1.1 Hz), 127.0,
126.3, 126.2, 123.8 (q, J = 274.8 Hz), 115.2, 101.4 (q, J = 34.1 Hz), 33.6, 30.0, 24.2, 24.1, 21.5.
19F NMR (282 MHz, CDCl3, CF3COOH-ext. st.):  (ppm) –60.5 (s, 3F). HRMS (APPI+-Obitrap)
m/z: [M]+. Calcd for C29H29F3 434.2216; Found 434.2226 (2.3 ppm).
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
1-(4-Bromophenyl)-1-(2,5-diisopropylphenyl)-3-phenyl-4,4,4-trifluoro-1,2-
CF3
butadiene (1n) was prepared according to general procedure B from 4-(4-
bromophenyl)-1,1,1-trifluoro-2,4-diphenylbut-3-yn-2-ol (10.2 mg, 0.28 mmol)
and diisopropylbenzene (267 µL, 1.411 mmol, 5.0 equiv) with 4.5 mg (0.028
Br
mmol) of FeCl3, in 0.56 mL of HFIP. The reaction mixture was stirred at ambient
temperature for 10 min. Purification by flash column chromatography over silica (petroleum ether)
1
gave 56 mg (40% yield) of yellow solid. Rf = 0.87 (petroleum ether/EtOAc 9:1). H NMR (400
MHz, CDCl3): δ (ppm) 7.55–7.47 (m, 2H), 7.44–7.28 (m, 7H), 7.25–7.19 (m, 2H), 7.14–7.08 (m,
1H), 2.98 (sept, J = 6.8 Hz, 1H), 2.90 (sept, J = 6.9 Hz, 1H), 1.25 (d, J = 6.9 Hz, 6H), 1.12 (d, J =
6.8 Hz, 3H), 1.00 (d, J = 6.8 Hz, 3H). 13C{1H} NMR (125 MHz, CDCl3): δ (ppm) 205.4 (q, J =
4.2 Hz), 146.8, 145.0, 134.3, 132.1, 131.7, 129.1, 129.0, 128.8, 128.7, 128.2, 127.4, 127.3, 126.3,
19
123.3 (q, J = 275.0 Hz), 122.7, 117.0, 103.1 (q, J = 34.8 Hz), 33.7, 30.4, 24.4, 24.1. F NMR
(376.5 MHz, CDCl3, CF3COOH-ext. st.):  (ppm) –58.8 (s, 3F). HRMS (APPI+-Orbitrap) m/z:
[M]+. Calcd for C28H2679BrF3 498.1165; Found 498.1168 (0.6 ppm).
1-(4-Bromophenyl)-1-(2,5-diisopropylphenyl)-3-phenyl-4,4,4-trifluoro-1,2-
butadiene (1o) was prepared according to general procedure B from 4-(4-
CF3
bromophenyl)-1,1,1-trifluoro-2-phenylbut-3-yn-2-ol (111 mg, 0.314 mmol) and
diisopropylbenzene (297 µL, 1.568 mmol, 5.0 equiv) with 4.7 mg (0.031 mmol) of
Br
FeCl3, in 0.63 mL of HFIP. The reaction mixture was stirred at ambient temperature for 3 h.
Purification by flash column chromatography over silica (petroleum ether) gave 111 mg (70%
yield) of a colorless oil. Rf = 0.88 (petroleum ether/EtOAc 9:1). 1H NMR (500 MHz, CDCl3): δ
(ppm) 7.52 (d, J = 7.7 Hz, 2H), 7.47 (d, J = 8.6 Hz, 2H), 7.42–7.36 (m, 2H), 7.36–7.31 (m, 2H),
7.31–7.27 (m, 1H), 7.15-7.10 (m, 3H), 2.98 (sept, J = 6.9 Hz, 1H), 2.92 (sept, J = 6.9 Hz, 1H),
1.26 (d, J = 6.9 Hz, 6H), 1.13 (d, J = 6.8 Hz, 3H), 1.03 (d, J = 6.9 Hz, 3H). 13C{1H} NMR (125
MHz, CDCl3): δ (ppm) 206.3 (q, J = 3.9 Hz), 146.9, 145.0, 133.8, 132.1, 131.6, 129.7, 129.0,
128.8, 128.7, 128.2, 127.5, 127.3, 126.3, 123.4 (q, J = 273.5 Hz), 122.7, 115.7, 104.3 (q, J = 34.2
ACS Paragon Plus Environment

Page 21 of 39
The Journal of Organic Chemistry
1
2
3
4
5
6
Hz), 33.7, 30.4, 24.4, 24.1, 24.1, 24.1. 19F NMR (282 MHz, CDCl3, CF3COOH-ext. st.):  (ppm)
–60.8 (s, 3F). HRMS (APPI+-Orbitrap) m/z: [M]+. Calcd for C28H2679BrF3 498.1165; Found
498.1175 (2.0 ppm).
7
8
9
1-(2-(5-Fluoro-m-xylenyl))-1,3-diphenyl-4,4,4-trifluoro-1,2-butadiene (1p) was
prepared according to modified general procedure B from 1,1,1-trifluoro-2,4-
F
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
CF3
diphenylbut-3-yn-2-ol (104 mg, 0.376 mmol) and 5-fluoro-m-xylene (142 µL, 1.13
mmol, 3.0 equiv) with 6.1 mg (0.038 mmol) of FeCl3, in 1.50 mL of HFIP. The
reaction mixture was heated at 80 °C for 24 h. Purification by flash column chromatography over
silica (petroleum ether) gave 37 mg (25% yield) of colorless oil. Rf = 0.84 (petroleum ether/EtOAc
9:1). 1H NMR (500 MHz, CDCl3): δ (ppm) 7.48 (d, J = 7.4 Hz, 2H), 7.40–7.29 (m, 6H), 7.25–7.20
(m, 2H), 6.84 (d, J = 9.4 Hz, 2H), 2.20 (s, 6H). 13C{1H} NMR (125 MHz, CDCl3): δ (ppm) 205.1
(q, J = 3.8 Hz), 162.4 (d, J = 244.7 Hz), 139.7 (d, J = 7.2 Hz), 132.9, 129.9, 129.3, 129.0, 128.8,
128.7, 128.6 (d, J = 2.0 Hz), 127.6 (q, J = 1.1 Hz), 126.6, 123.6 (q, J = 273.5 Hz), 114.6 (d, J =
21.0 Hz), 113.5, 104.3 (q, J = 34.3 Hz), 20.6. 19F NMR (282 MHz, CDCl3, CF3COOH-ext. st.): 
(ppm) –60.1 (s, 3F), –115.9 (s, 1H). HRMS (APPI+-Orbitrap) m/z: [M]+. Calcd for C24H18F4
382.1339; Found 382.1348 (2.4 ppm).
(1-(2,6-Dichloro-4-methylphenyl)-1,3-diphenyl-4,4,4-trifluoro-1,2-butadiene (1q)
was prepared according to modified general procedure B from 1,1,1-trifluoro-2,4-
Cl
CF3
Cl
diphenylbut-3-yn-2-ol (108 mg, 0.392 mmol) and 3,5-dichlorotoluene (190 mg, 1.18
mmol, 3.0 equiv) with 6.4 mg (0.039 mmol) of FeCl3, in 1.57 mL of HFIP. The
reaction mixture was heated at 80 °C for 24 h. Purification by flash column chromatography over
1
silica (petroleum ether) gave 31 mg (23% yield) of white solid. H NMR (500 MHz, CDCl3): δ
(ppm) 7.56 (d, J = 7.1 Hz, 2H), 7.41–7.30 (m, 7H), 7.24–7.19 (m, 3H), 2.27 (s, 3H). 7.56 (d, J =
13
7.1 Hz, 2H), 7.41–7.30 (m, 7H), 7.24–7.19 (m, 3H), 2.27 (s, 3H). C{1H} NMR (125 MHz,
CDCl3): δ (ppm) 205.3 (q, J = 3.9 Hz), 141.1, 135.3, 134.7, 132.1, 131.0, 129.3, 129.1, 129.0,
128.9, 127.7(q, J = 1.2 Hz), 127.3, 126.5, 123.4 (q, J = 273.9 Hz), 112.8, 106.6 (q, J = 34.2 Hz),
19
20.6. F NMR (282 MHz, CDCl3, CF3COOH-ext. st.):  (ppm) –60. (s, 3F). HRMS (APPI+-
Orbitrap) m/z: [M]+. Calcd for C23H15Cl2F3 418.0497; Found 418.0500 (0.7 ppm).
Cl
Cl
(1-(2,4-Dichloro-5-methylphenyl)-1,3-diphenyl-4,4,4-trifluoro-1,2-butadiene (1q')
was prepared according to modified general procedure B from 1,1,1-trifluoro-2,4-
diphenylbut-3-yn-2-ol (108 mg, 0.392 mmol) and 3,5-dichlorotoluene (190 mg, 1.18
mmol, 3.0 equiv) with 6.4 mg (0.039 mmol) of FeCl3, in 1.57 mL of HFIP. The
CF3
reaction mixture was heated at 80 °C for 24 h. Purification by flash column chromatography over
silica (petroleum ether) gave 17 mg (10% yield) of white solid1H NMR (500 MHz, CDCl3) δ (ppm)
7.57 (d, J = 7.1 Hz, 2H), 7.43 – 7.31 (m, 7H), 7.25 – 7.20 (m, 3H), 2.27 (s, 3H). 13C{1H} NMR
(125 MHz, CDCl3): δ (ppm) 205.3 (q, J = 3.9 Hz), 141.1, 135.3, 134.7, 132.1, 131.0, 129.3, 129.1,
129.0, 128.9, 127.7(q, J = 1.2 Hz), 127.3, 126.5, 123.4 (q, J = 273.9 Hz), 112.8, 106.6 (q, J = 34.2
Hz), 20.6. 19F NMR (282 MHz, CDCl3, CF3COOH-ext. st.):  (ppm) –60.8 (s, 3F). HRMS (APPI+-
Orbitrap) m/z [M]+. Calcd for C23H15Cl2F3 418.0497; Found 418.0500 (0.7 ppm).
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 22 of 39
1
2
3
4
5
6
7
8
9
3-(4-Bromophenyl)-1-durenyl-1,3-diphenyl-4,4,4-trifluoro-1,2-butadiene (1s) was
prepared according to modified general procedure B 4-(4-bromophenyl)-1,1,1-
trifluoro-2,4-diphenylbut-3-yn-2-ol (101 mg, 0.284 mmol) and durene (114 mg,
0.85 mmol, 3.0 equiv.) with 2.9 mg (0.028 mmol) of FeCl3, in 1.13 mL of HFIP.
The reaction mixture was heated at 80 °C for 3 h. Purification by flash column
CF3
Br
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
chromatography over silica (petroleum ether) gave 125 mg (93% yield) of white solid. Rf = 0,90
(petroleum ether/EtOAc 9:1). 1H NMR (400 MHz, CDCl3): δ (ppm) 7.49 (dd, J = 8.8, 2.0 Hz, 2H),
7.39–7.30 (m, 5H), 7.24–7.17 (m, 2H), 7.03 (s, 1H), 2.26 (s, 3H), 2.24 (s, 3H), 2.14 (s, 3H), 2.06
(s, 3H). 13C{1H} NMR (100 MHz, CDCl3): δ (ppm) 205.0 (q, J = 3.6 Hz), 134.6, 134.2, 133.2,
132.6, 132.5, 132.1, 131.7, 129.4, 129.2, 128.8, 126.9, 123.6 (q, J = 275.2 Hz), 122.7, 115.8, 103.2
(q, J = 34.8 Hz), 20.2 (2C), 17.5, 16.7. 19F NMR (376.5 MHz, CDCl3, CF3COOH-ext. st.):  (ppm)
–59.0 (s, 3F). HRMS (APPI+-Orbitrap) m/z: [M]+. Calcd for C26H2279BrF3 470.0851; Found
470.0862 (2.3 ppm).
Characterization data for indenes
3-Mesityl-1-phenyl-1-(trifluoro-methyl)-1H-indene (2a) was prepared according to
general procedure C from 1,1,1-trifluoro-2,4-diphenylbut-3-yn-2-ol (106 mg, 0.382
F3C
mmol) and mesitylene (160 µL, 1.15 mmol, 3.0 equiv) with 6.2 mg (0.038 mmol) of
FeCl3, in 1.50 mL of HFIP. The reaction mixture was heated at 80 °C for 24 h.
Purification by flash column chromatography over silica (petroleum ether) gave 137
1
mg (94% yield) of a colorless oil. Rf = 0.80 (petroleum ether/EtOAc 9:1). H NMR (400 MHz,
CDCl3): δ (ppm) 7.68–7.61 (m, 1H), 7.61–7.55 (m, 2H), 7.38–7.29 (m, 5H), 6.98 (s, 1H), 6.94 (s,
1H), 6.93–6.90 (m, 1H), 6.44 (s, 1H), 2.35 (s, 3H), 2.15 (s, 3H), 2.05 (s, 3H). 13C{1H} NMR (125
MHz, CDCl3):  (ppm) 147.1, 145.0, 143.5, 137.6, 136.9, 136.5, 135.0, 133.4, 130.5, 128.9, 128.8,
128.4, 128.2, 128.1, 127.8, 126.9 (q, J = 280.6 Hz), 126.7, 125.4, 121.4, 64.8 (q, J = 26.6 Hz),
21.3, 20.3, 20.0. 19F NMR (282 MHz, CDCl3, CF3COOH-ext. st.):  (ppm) –68.2 (s, 3F). HRMS
(APPI+-Orbitrap) m/z: [M]+. Calcd for C25H21F3 378.1590; Found 378.1593 (0.8 ppm).
D
D
F3C
4,5,6,7-Tetradeutero-3-mesityl-1-phenyl-1-(trifluoro-methyl)-1H-indene (2a-d4) was
prepared according to general procedure C from 1,1,1-trifluoro-2-phenyl-4-
pentadeuterophenyl-but-3-yn-2-ol (68.4 mg, 0.243 mmol) and mesitylene (102 µL,
0.73 mmol, 3.0 equiv) with 3.9 mg (0.024 mmol) of FeCl3 in 0.97 mL of HFIP. The
Ph
D
D
reaction mixture was heated at 80 °C for 24 h. Purification by flash column chromatography over
silica (petroleum ether) gave 37 mg (39% yield) of a colorless oil. Rf = 0.80 (petroleum
ether/EtOAc 9:1). 1H NMR (400 MHz, CDCl3): δ (ppm) 7.62–7.56 (m, 2H), 7.41–7.29 (m, 3H),
2
6.99 (s, 1H), 6.95 (s, 1H), 6.45 (s, 1H), 2.36 (s, 3H), 2.17 (s, 3H), 2.07 (s, 3H). H NMR (600
MHz, CH2Cl2): δ (ppm) 7.71 (br. s, 1D), 7.38 (br. s, 2D), 6.94 (br. s, 1D). HRMS (ESI-TOF) m/z:
[M+H]+ Calcd for C25H18D4F3 383.1919; Found 383.1918 (0.3 ppm).
ACS Paragon Plus Environment

Page 23 of 39
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
3-Mesityl-1,6-diphenyl-1-(trifluoromethyl)-1H-indene
(2c)
was
prepared
F3C
according to modified general procedure C from 4-((1,1'-biphenyl)-4-yl)-1,1,1-
trifluoro-2-phenylbut-3-yn-2-ol (70 mg, 0.20 mmol) and mesitylene (84 µL, 0.60
mmol, 3.0 equiv) with 3.3 mg (0.020 mmol) of FeCl3, in 0.41 mL of HFIP. The
reaction mixture was heated at 50 °C for 6 h. Purification by flash column
chromatography over silica (petroleum ether) gave 82 mg (91% yield) of the product (in 90%
purity). 1H NMR (400 MHz, CDCl3): δ (ppm) 7.84 (s, 1H), 7.68-7.57 (m, 4H), 7.54 (dd, J = 7.9,
1.6 Hz, 1H), 7.47-7.40 (m, 2H), 7.38-7.30 (m, 4H), 7.03-6.93 (m, 3H), 6.46 (s, 1H), 2.35 (s, 3H),
2.18 (s, 3H), 2.09 (s, 3H). 13C{1H} NMR (100 MHz, CDCl3):  (ppm) 146.9, 144.4, 144.2, 144.1,
140.1, 137.7, 136.9, 136.5, 135.0, 133.7, 130.5, 129.0, 128.9, 128.5, 128.3, 128.2, 128.0, 127.8,
127.5, 127.4, 126.9 (q, J = 280.8 Hz), 124.4, 121.6, 65.4 (q, J = 26.6 Hz), 21.3, 20.4, 20.1. F
NMR (376.5 MHz, CDCl3):  (ppm) –65.9 (s, 3F). HRMS (APPI+-Orbitrap) m/z [M]+. Calcd for
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
19
C31H25F3 454.1903; Found 454.1904 (0.2 ppm).
3-Mesityl-6-methyl-1-phenyl-1-(trifluoromethyl)-1H-indene (2d) was prepared
according to modified general procedure C from 1,1,1-trifluoro-2-phenyl-4-(p-
F3C
toluyl)but-3-yn-2-ol (80 mg, 0.28 mmol) and mesitylene (117 µL, 0.84 mmol, 3.0
equiv) with 4.5 mg (0.028 mmol) of FeCl3, in 0.55 mL of HFIP. The reaction mixture
was heated at 50 °C for 6 h. Purification by flash column chromatography over silica
(petroleum ether) gave 98 mg (91% yield) of the product. 1H NMR (400 MHz, CDCl3): δ (ppm)
7.65 (d, J = 7.3 Hz, 2H), 7.52 (s, 1H), 7.44-7.33 (m, 3H), 7.19 (d, J = 7.7 Hz, 1H), 7.04 (s, 1H),
7.00 (s, 1H), 6.88 (d, J = 7.6 Hz, 1H), 6.43 (s, 1H), 2.47 (s, 3H), 2.40 (s, 3H), 2.23 (s, 3H), 2.13
(s, 3H). C{1H} NMR (100 MHz, CDCl3):  (ppm) 147.0, 143.9, 142.4, 137.5, 136.9, 136.7,
136.5, 135.3, 132.5, 130.7, 129.6, 128.8, 128.4, 128.2, 128.0, 127.8, 127.0 (q, J = 280.9 Hz), 126.3,
121.1, 64.7 (q, J = 26.3 Hz), 21.8, 21.2, 20.3, 20.0. 19F NMR (376.5 MHz, CDCl3):  (ppm) –66.0
(s, 3F). HRMS (ESI-TOF) m/z: [M+H]+ Calcd for C26H24F3 393.1825; Found 393.1815 (2.5 ppm).
13
3-Mesityl-1-toluyl-1-(trifluoromethyl)-1H-indene (2f) was prepared according to
general procedure C from 1,1,1-trifluoro-4-phenyl-2-(p-tolulyl)but-3-yn-2-ol (93 mg,
F3C
0.32 mmol) and mesitylene (133 µL, 0.96 mmol, 3.0 equiv) with 5.1 mg (0.032 mmol)
of FeCl3, in 1.27 mL of HFIP. The reaction mixture was stirred at ambient temperature
for 3 h. Purification by flash column chromatography over silica (petroleum ether)
gave 120 mg (96% yield) of colorless oil. Rf = 0.83 (petroleum ether/EtOAc 9:1). 1H NMR (500
MHz, CDCl3) δ (ppm) 7.67–7.64 (m, 1H), 7.48 (d, J = 8.0 Hz, 2H), 7.34–7.28 (m, 2H), 7.16 (d, J
= 8.1 Hz, 2H), 6.99 (s, 1H), 6.95 (s, 1H), 6.93–6.90 (m, 1H), 6.44 (s, 1H), 2.35 (s, 3H), 2.34 (s,
13
3H), 2.16 (s, 3H), 2.06 (s, 3H). C{1H} NMR (125 MHz, CDCl3) δ (ppm) 146.9, 144.9, 143.6,
137.9, 137.6, 136.9, 136.5, 133.5, 131.9, 130.6, 129.5, 128.8, 128.4, 128.2, 127.7, 126.9 (q, J =
282.5 Hz), 126.6, 125.4, 121.3, 64.5 (q, J = 26.7 Hz), 21.2, 21.1, 20.3, 20.0. 19F NMR (376.5 MHz,
CDCl3, C6F6-ext. st.):  (ppm) –68.4 (s, 3F). HRMS (APPI+-Orbitrap) m/z: [M]+. Calcd for
C26H23F3 392.1746; Found 392.1747 (0.3 ppm).
3-Mesityl-1-(4-methoxyphenyl)-1-(trifluoromethyl)-1H-indene (2j) was prepared
according to modified general procedure C from 1,1,1-trifluoro-2-(4-
OMe
F3C
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 24 of 39
1
2
3
4
5
6
7
8
9
metoxyphenyl)-4-phenylbut-3-yn-2-ol (109 mg, 0.356 mmol) and mesitylene (149 µL, 1.07 mmol,
3.0 equiv) with 5.8 mg (0.036 mmol) of FeCl3, in 1.42 mL of HFIP. The reaction mixture was
heated at 80 °C for 1 h. Purification by flash column chromatography over silica (petroleum
ether/EtOAc 40:1 to 30:1) gave 131 mg (90% yield) of yellow oil. Rf = 0.58 (petroleum
1
ether/EtOAc 9:1). H NMR (400 MHz, CDCl3) δ ppm 7.69–7.63 (m, 1H), 7.54–7.48 (d, J = 8.8
Hz, 2H), 7.31 (dd, J = 5.5, 3.1 Hz, 2H), 6.98 (s, 1H), 6.94 (s, 1H), 6.91 (dd, J = 5.5, 3.2 Hz, 1H),
6.87 (d, J = 8.9 Hz, 2H), 6.43 (s, 1H), 3.80 (s, 3H), 2.35 (s, 3H), 2.15 (s, 3H), 2.04 (s, 3H). 13C{1H}
NMR (100 MHz, CDCl3) δ (ppm) 159.3, 146.8, 144.9, 143.6, 137.6, 136.9, 136.5, 133.5, 130.6,
129.1, 128.8, 128.4, 128.2, 126.7, 126.9 (q, J = 282.5 Hz), 126.6, 125.4, 121.4, 114.1, 64.2 (q, J =
26.8 Hz), 55.4, 21.2, 20.3, 20.0. 19F NMR (376.5 MHz, CDCl3, CF3COOH-ext. st.):  (ppm) –66.6
(s, 3F). HRMS (APPI+-Orbitrap): m/z: [M]+. Calcd for C26H23F3O 408.1696; Found 408.1697 (0.2
ppm).
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
3-Mesityl-5-methoxy-1-phenyl-1-(trifluoromethyl)-1H-indene (2k) was prepared
according to general procedure C from 1,1,1-trifluoro-4-metoxyphenyl-2-
F3C
MeO
phenylbut-3-yn-2-ol (106 mg, 0.345 mmol) and mesitylene (144 µL, 1.03 mmol,
3.0 equiv) with 5.6 mg (0.035 mmol) of FeCl3, in 1.03 mL of HFIP. The reaction
mixture was heated at 80 °C for 24 h. Purification by flash column chromatography
over silica (petroleum ether/EtOAc 40:1 to 30:1) gave 84 mg (60% yield) of acolorless oil. Rf =
0.74 (petroleum ether/EtOAc 9:1). 1H NMR (400 MHz, CDCl3) δ 7.56 (d, J = 7.8 Hz, 2H), 7.35–
7.25 (m, 3H), 7.19 (s, 1H), 6.95 (s, 1H), 6.91 (s, 1H), 6.80 (s, 2H), 6.28 (s, 1H), 3.78 (s, 3H), 2.31
(s, 3H), 2.14 (s, 3H), 2.06 (s, 3H). 13C{1H} NMR (100 MHz, CDCl3): δ (ppm) 159.1, 146.7, 145.4,
137.8, 137.5, 136.9, 136.5, 135.2, 131.4, 130.8, 128.8, 128.4, 128.2, 128.1, 127.7, 126.9 (q, J =
282.5 Hz), 121.8, 113.5, 112.7, 64.7 (q, J = 26.7 Hz), 55.7, 21.2, 20.3, 20.0. 19F NMR (376.5 MHz,
CDCl3, CF3COOH-ext. st.):  (ppm) –74.9 (s, 3F). HRMS (APPI+-Orbitrap) m/z: [M]+. Calcd for
C26H23F3O 408.1696; Found 408.1695 (–0.2 ppm).
3-(2,5-Diisopropylphenyl)-1-phenyl-1-(trifluoromethyl)-1H-indene (2l) was prepared
according to general procedure C from 1,1,1-trifluoro-2,4-diphenylbut-3-yn-2-ol (104
F3C
mg, 0.375 mmol) and diizopropyl benzene (213 µL, 1.13 mmol, 3.00 equiv) with 6.1
mg (0.038 mmol) of FeCl3, in 0.75 mL of HFIP. The reaction mixture was stirred at
ambient temperature for 3 h. Purification by flash column chromatography over silica
(petroleum ether) gave 142 mg (90% yield) of a white solid. Rf = 0.91 (petroleum ether/EtOAc
9:1). 1H NMR (500 MHz, CDCl3) δ (ppm) 7.37–7.20 (m, 11H), 7.17 (d, J = 8.3 Hz, 1H), 6.15 (s,
1H), 2.94–2.85 (m, 2H), 1.15 (d, J = 6.8 Hz, 3H), 1.00 (d, J = 7.4 Hz, 3H), 0.98 (d, J = 7.4 Hz,
3H), 0.66 (d, J = 6.7 Hz, 3H). 13C{1H} NMR (126 MHz, CDCl3) δ (ppm) 148.5, 143.7, 141.8,
141.1, 141.0, 138.1, 136.4 (q, J = 2.1 Hz), 134.8, 131.9, 128.7 (q, J = 2.0 Hz), 128.2, 128.1, 127.9,
127.8, 126.7, 126.8 (q, J = 283.5 Hz), 126.1, 125.7, 121.5, 64.4 (q, J = 26.4 Hz), 29.3, 27.1, 24.3,
23.9, 23.6, 23.4. 19F NMR (376.5 MHz, CDCl3, CF3COOH-ext. st.): δ (ppm) –63.7 (s, 3F). HRMS
(APPI+-Orbitrap) m/z: [M]+. Calcd for C28H27F3 420.2059; Found 420.2061 (1.9 ppm).
ACS Paragon Plus Environment

Page 25 of 39
The Journal of Organic Chemistry
1
2
3
4
5
6
Br
1-(4-Bromophenyl)-3-(2,5-diisopropylphenyl)-1-(trifluoromethyl)-1H-indene (2n)
was prepared according to modified general procedure C from 4-(4-bromophenyl)-
F3C
1,1,1-trifluoro-2,4-diphenylbut-3-yn-2-ol
(102
mg,
0.288
mmol)
and
7
8
9
diisopropylbenzene (164 µL, 0.87 mmol, 3.0 equiv) with 4.7 mg (0.029 mmol) of
FeCl3, in 1.15 mL of HFIP. The reaction mixture was heated at 80 °C for 1 h.
Purification by flash column chromatography over silica (with petroleum ether) gave
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
111 mg (77% yield) of yellow solid. Rf = 0.88 (petroleum ether/EtOAc 9:1). 1H NMR (500 MHz,
CDCl3): δ (ppm) 7.57–7.29 (m, 8H), 7.22–7.12 (m, 3H), 6.11 (s, 1H), 2.88 (sept, J = 6.4 Hz, 2H),
1.17 (d, J = 6.8 Hz, 3H), 1.02 (d, J = 6.8 Hz, 3H), 0.99 (d, J = 6.8 Hz, 3H), 0.74 (d, J = 6.8 Hz,
3H). 13C{1H} NMR (126 MHz, CDCl3) δ (ppm) 148.5, 143.7, 141.8, 141.1, 141.0, 138.1, 136.4
(q, J = 1.7 Hz), 134.8, 131.9, 128.7 (q, J = 1.7 Hz), 128.2, 128.1, 127.9, 127.8, 126.8 (q, J = 281.8
Hz), 126.7, 126.1, 125.7, 121.5, 64.4 (q, J = 26.4 Hz), 29.4, 27.1, 24.3, 23.9, 23.6, 23.4z.19F NMR
(376.5 MHz, CDCl3, CF3COOH-ext. st.):  (ppm) –64.5 (s, 3F). HRMS (APPI+-Orbitrap): m/z for
C28H2681BrF3 [M]+.: calculated 500.1150; found 500.1145 (–1.0 ppm).
3-(4-(1-Chloro-3,5-dimethylphenyl))-1-phenyl-1-(trifluoro-methyl)-1H-indene
(2s)
F3C
was prepared according to a modification of general procedure B from 1,1,1-trifluoro-
2,4-diphenylbut-3-yn-2-ol (113 mg, 0.410 mmol) and 5-chloro-m-xylene (165 µL, 1.23
mmol, 3.0 equiv) with 6.1 mg (0.041 mmol) of FeCl3, in 1.6 mL of HFIP. The reaction
mixture was heated at 80 °C for 24 h. Purification by flash column chromatography over
Cl
silica (petroleum ether) gave 31 mg (19 % yield) of a white solid. Rf = 0.31 (petroleum ether). 1H
NMR (500 MHz, CDCl3): δ (ppm): 7.64 (d, J = 6.8 Hz, 1H), 7.55 (d, J = 6.8 Hz, 2H), 7.37–7.27
(m, 5H), 7.16 (s, 1H), 6.98 (s, 1H), 6.95–6.91 (m, 1H), 6.51 (s, 1H), 2.33 (s, 3H), 2.05 (s, 3H).
13C{1H} NMR (125 MHz, CDCl3): δ (ppm) 144.7, 144.4, 143.2, 139.3, 138.6, 134.8, 134.6, 133.8,
129.7, 129.3, 128.9, 128.8, 128.2, 127.8, 127.7, 126.7, 126.7 (q, J = 281.1 Hz), 125.5, 121.4, 65.0
(q, J = 26.8 Hz), 21.1, 20.6. 19F NMR (282 MHz, CDCl3, CF3COOH-ext. st.):  (ppm) –67.7 (s,
3F). HRMS (APPI+-Orbitrap) m/z: [M]+. calculated for C24H1835ClF3 398.1044; found 398.1050
(1.5 ppm).
1-Phenyl-3-(2,4,6-triethylphenyl)-1-(trifluoromethyl)-1H-indene (2x) was prepared
according to general procedure C from 1,1,1-trifluoro-2,4-diphenylbut-3-yn-2-ol (117
F3C
mg, 0.424 mmol) and 1,3,5-triethylbenzene (239 µL, 1.27 mmol, 3.0 equiv) with 6.9
mg (0.042 mmol) of FeCl3, in 1.69 mL of HFIP. The reaction mixture was heated at 80
°C for 24 h. Purification by flash column chromatography over silica (petroleum ether)
gave 127 mg (71% yield) of colorless oil. Rf = 0.88 (petroleum ether/EtOAc 9:1). 1H NMR (500
MHz, CDCl3) δ (ppm) 7.67–7.62 (m, 1H), 7.57 (d, J = 6.9 Hz, 2H), 7.36–7.29 (m, 5H), 7.03 (s,
1H), 7.00 (s, 1H), 6.96–6.91 (m, 1H), 6.48 (s, 1H), 2.69 (q, J = 7.6 Hz, 2H), 2.57–2.27 (m, 4H),
1.30 (t, J = 7.6 Hz, 3H), 1.09 (t, J = 7.5 Hz, 3H), 0.98 (t, J = 7.5 Hz, 3H). 13C{1H} NMR (125
MHz, CDCl3) δ (ppm) 146.4, 146.1, 144.3, 143.3, 143.3, 142.9, 134.9, 133.9, 129.4, 128.9, 128.8,
128.1, 127.8, 126.9 (q, J = 282.5 Hz), 126.7, 125.7, 125.5, 125.3, 121.6, 64.8 (q, J = 26.7 Hz),
28.9, 27.0, 26.9, 16.3, 16.2, 15.6. 19F NMR (282 MHz, CDCl3, CF3COOH-ext. st.):  (ppm) –67.9
(s, 3F). HRMS (APPI+-Orbitrap) m/z: [M]+. Calcd for C28H27F3 420.2059; Found 420.2055 (–1.2
ppm).
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 26 of 39
1
2
3
4
5
6
7
8
9
OMe
3-(2,4,6-Trimethoxyphenyl)-1-(4-methoxyphenyl)-1-(trifluoromethyl)-1H-indene
(2y) was prepared according to a modification of general procedure C from 1,1,1-
trifluoro-2-(4-metoxyphenyl)-4-phenylbut-3-yn-2-ol (258 mg, 0.841 mmol) and
1,3,5-trimethoxybenzene (424 mg, 2.52 mmol, 3.0 equiv) with 13.6 mg (0.084
mmol) of FeCl3, in 3.4 mL of HFIP. The reaction mixture was heated at 120 °C
F3C
OMe
MeO
OMe
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
for 24 h in a high-pressure reaction tube. Purification by flash column chromatography over silica
(petroleum ether/EtOAc 40:1 to 30:1) gave 364 mg (95% yield) of a yellow solid. Rf = 0.21
(petroleum ether/EtOAc 9:1). 1H NMR (500 MHz, CDCl3) δ (ppm) 7.64–7.58 (m, 3H), 7.30 (td, J
= 1.0, 7.5 Hz, 1H), 7.26 – 7.22 (m, 1H), 7.04 (d, J = 7.5 Hz, 1H), 6.91 – 6.84 (m, 2H), 6.58 (s,
1H), 6.26 (s, 2H), 3.89 (s, 3H), 3.79 (s, 3H), 3.76–3.70 (m, 6H).13C{1H} NMR (126 MHz, CDCl3)
δ (ppm) 161.5, 159.4, 159.3, 159.1, 145.4, 143.5, 139.8, 135.3 (q, J = 1.8 Hz), 129.1 (q, J = 1.8
Hz), 128.2, 127.4, 127.0 (q, J = 282.4 Hz), 125.8, 124.7, 121.9, 113.9, 104.8, 91.2, 91.1, 63.9 (q,
J = 26.8 Hz), 56.2, 55.9, 55.5, 55.3. 19F NMR (282 MHz, CDCl3, CF3COOH-ext. st.):  (ppm) –
66.7 (s, 3F). HRMS (ESI-Orbitrap) m/z: [M+H]+ Calcd for C26H24 F3O4 457.1621; Found 457.1611
(–2.2 ppm).
Preparation of tertiary propargylic alcohols for synthesis of chromenes
General procedure D:33 Step 1. To a 0.5 M solution of ethynyl magnesium bromide (10 mmol)
in THF was slowly added aryl trifluoromethyl ketone (10 mmol) in THF (20 mL). After 3 h at
ambient temperature the reaction mixture was quenched first with water and then with saturated
NH4Cl(aq). The aqueous layer was extracted with Et2O. The combined organic layers were dried
over Na2SO4, filtered and concentrated under reduced pressure to afford colored oil (2-aryl-1,1,1-
trifluoro-3-butyn-2-ol - compound A) that was engaged in the next step without further
purification. Step 2. To a solution of 2-iodophenol (10 mmol) and imidazole (20 mmol) in dry
THF (20 mL) was added tert-butyldimethylsilyl chloride (20 mmol) in one portion and the reaction
mixture was stirred at ambient temperature for 1 h. The mixture was then diluted with CH2Cl2 and
filtered through celite. The residue was purified by flash column chromatography (petroleum
ether) to provide the desired product (1-iodo-2-(tert-butyldimethylsilyloxy)benzene - compound
B). Step 3. To a stirred solution of compound B (10 mmol) in Et3N (20 mL) under argon were
sequentially added Pd(PPh3)2Cl2 (1 mol %) and CuI (2 mol %) at ambient temperature. Then
compound A (1.3 equiv) was added and the mixture was stirred overnight. The reaction was
quenched with saturated NH4Cl (aq), extracted with Et2O, dried over Na2SO4, and was purified by
flash column chromatography (petroleum ether/EtOAc 9:1). To the isolated product (10 mmol) in
THF (20 mL) was added tetra-n-butyl ammonium fluoride (1.2 equiv) at room temperature for 30
min. The reaction was quenched by adding water and extracted with EtOAc, dried over Na2SO4.
The crude material was purified by column chromatography (petroleum ether/EtOAc 10:1) to give
the pure propargylic alcohol that was used for subsequent synthesis of chromenes.
2-(4,4,4-Trifluoro-3-hydroxy-3-phenylbut-1-yn-1-yl)phenol was prepared according
to general procedure D using 2,2,2-trifluoro-1-phenylethan-1-one (1.4 mL, 10 mmol).
HO
Ph
CF3
OH
ACS Paragon Plus Environment

Page 27 of 39
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
Purification by flash column chromatography over silica (petroleum ether/EtOAc 9:1) gave 263
mg (90% yield) of light yellow yellow solid. Mp: 92–93 oC. 1H NMR (400 MHz, CDCl3): δ (ppm)
7.85-7.76 (m, 2H), 7.47-7.44 (m, 3H), 7.42 (dd, J = 7.7, 1.6 Hz, 1H), 7.33 (ddd, J = 8.2, 7.5, 1.5
Hz, 1H), 6.98 (dd, J = 7.6, 0.7 Hz, 1H), 6.92 (td, J = 7.6, 1.1 Hz, 1H), 5.57 (s, 1H), 3.16 (s, 1H).
13C{1H} NMR (100 MHz, CDCl3): δ (ppm) 157.4, 135.0, 132.5, 132.0, 129.9, 128.6, 127.2, 123.4
(q, J = 285.6 Hz), 120.8, 115.5, 107.4, 91.6, 82.9, 73.7 (q, J = 32.8 Hz). 19F NMR (376.5 MHz,
CDCl3, CF3CO2H - ext. st.): δ (ppm) –81.1 (s, 3F). HRMS (APPI+-Orbitrap) m/z: [M+H]+ Calcd
for C16H12O2F3 293.0784; Found 293.0783 (–0.2 ppm).
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
2-(4,4,4-Trifluoro-3-hydroxy-3-(p-tolyl)but-1-yn-1-yl)phenol
was
prepared
HO
CF3
according to general procedure D using 2,2,2-trifluoro-1-(p-tolyl)ethan-1-one (1.5
mL, 10 mmol). Purification by flash column chromatography over silica
(petroleum ether/EtOAc 9:1) gave 110 mg (36% yield) of brown oil. 1H NMR (400
OH
MHz, CDCl3): δ (ppm) 7.68 (d, J = 8.2 Hz, 2H), 7.41 (dd, J = 7.7, 1.4 Hz, 1H), 7.36–7.30 (m, 1H),
7.22-7.25 (m, 2H), 6.97 (d, J = 8.3 Hz, 1H), 6.92 (t, J = 7.6 Hz, 1H), 5.61 (s, 1H), 3.19 (s, 1H),
2.40 (s, 3H). 13C{1H} NMR (100 MHz, CDCl3): δ (ppm) 157.4, 140.0, 132.4, 132.2, 131.9, 129.3,
19
127.1, 123.5 (q, J = 285.8 Hz), 120.8, 115.5, 107.5, 91.8, 82.7, 73.6 (q, J = 31.6 Hz), 21.3. F
NMR (376.5 MHz, CDCl3, CF3CO2H - ext. st.): δ (ppm) –81.1 (s, 3F). HRMS (APPI+-Orbitrap)
m/z: [M]+. Calcd for C17H13O2F3 306.0862; Found 305.0862 (–0.1 ppm).
HO
2-(3-Hydroxy-3-(trifluoromethyl)pent-1-yn-1-yl)phenol was prepared according to
general procedure D using 1,1,1-trifluorobutan-2-one (1 g, 8 mmol). Purification by
Et
CF3
OH
flash column chromatography over silica (petroleum ether/EtOAc 9:1) gave 54 mg
1
(22% yield, 70% purity (remainder is 1,1,1-trifluorobutan-2-one) of brown oil. H NMR (400
MHz, CDCl3): δ (ppm) 7.36 (dd, J = 7.7, 1.6 Hz, 1H), 7.33 (ddd, J = 8.2, 7.5, 1.5 Hz, 1H), 6.96 (d,
J = 8.3 Hz, 2H), 6.90 (td, J = 7.6, 1.0 Hz, 1H), 5.57 (s, 1H), 2.70 (s, 1H), 1.98 (q, J = 7.6 Hz, 2H),
1.22 (t, J = 7.4 Hz, 3H). 13C{1H} NMR (100 MHz, CDCl3): δ (ppm) 157.0, 132.4, 131.7, 124.3 (q,
J = 285.2 Hz), 120.7, 115.4, 107.6, 90.4, 82.2, 73.2 (q, J = 31.1 Hz), 28.4, 7.9. 19F NMR (376.5
MHz, CDCl3, CF3CO2H - ext. st.): δ (ppm) –82.1 (s, 3F). HRMS (APPI+-Orbitrap) [M]+. Calcd
m/z: for C12H11O2F3 244.0711; Found 244.0705 (–2.5 ppm).
4-(2-((Tert-butyldimethylsilyl)oxy)phenyl)-1,1,1-trifluoro-2-(p-tolyl)but-3-yn-2-ol
HO
was prepared according to general procedure D using 2,2,2-trifluoro-1-(p-
CF3
tolyl)ethan-1-one (1.5 mL, 10 mmol), without deprotection step. Purification by
OTBS
flash column chromatography over silica (petroleum ether/EtOAc 9:1) gave 362
mg (86% yield) of brown oil. 1H NMR (400 MHz, CDCl3): δ (ppm) 7.69 (d, J = 8.1 Hz, 2H), 7.45
(dd, J = 7.7, 1.7 Hz, 1H), 7.28–7.19 (m, 3H), 6.93 (t, J = 7.5 Hz, 1H), 6.84 (d, J = 8.3 Hz, 1H),
13
3.02 (s, 1H), 2.38 (s, 3H), 0.97 (s, 9H), 0.24 (s, 3H), 0.23 (s, 3H). C{1H} NMR (100 MHz,
CDCl3): δ (ppm) 156.9, 139.3, 134.3, 132.5, 130.7, 128.9, 127.2, 123.1 (q, J = 285.3 Hz), 121.1,
19
119.2, 113.4, 87.8, 85.5, 73.3 (q, J = 31.9 Hz), 25.6, 21.3, 18.3, –4.2. F NMR (376.5 MHz,
CDCl3, CF3CO2H - ext. st.): δ (ppm) –78.9 (s, 3F). HRMS (APPI+-Orbitrap) m/z: [M+H]+.
calculated for C23H28O2F3Si 421.1805; Found 421.1797 (–2.0 ppm).
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 28 of 39
1
2
3
4
5
6
7
8
9
Br
2-(4-Bromophenyl)-4-(2-((tert-butyldimethylsilyl)oxy)phenyl)-1,1,1-trifluoro-
but-3-yn-2-ol was prepared according to general procedure D using 1-(4-
bromophenyl)-2,2,2-trifluoroethan-1-one (2.5 g, 10 mmol), without deprotection
HO
CF3
OTBS
step. Purification by flash column chromatography over silica (petroleum
1
ether/EtOAc 9:1) gave 427 mg (88% yield) of brown oil. H NMR (400 MHz, CDCl3): δ (ppm)
7.68 (d, J = 8.6 Hz, 2H), 7.54 (d, J = 8.6 Hz, 2H), 7.44 (dd, J = 7.7, 1.7 Hz, 1H), 7.28–7.25 (m,
1H), 6.93 (td, J = 7.6, 1.0 Hz, 1H), 6.84 (d, J = 8.3 Hz, 1H), 3.09 (s, 1H), 0.95 (s, 9H), 0.23 (s,
3H), 0.22 (s, 3H). 13C{1H} NMR (100 MHz, CDCl3): δ (ppm) 157.0, 134.9, 134.6, 131.7, 131.2,
129.4, 124.1, 123.4 (q, J = 286.4 Hz), 121.4, 119.8, 113.4, 87.4, 86.4, 73.4 (q, J = 32.8 Hz), 25.8,
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
19
18.5, –3.9. F NMR (376.5 MHz, CDCl3, CF3CO2H - ext. st.): δ (ppm) –81.0 (s, 3F). HRMS
(APPI+-Orbitrap) m/z [M]+. Calcd for C22H25O2 BrF3Si 485.0754; Found 485.0756 (0.4 ppm).
79
General procedure E for synthesis of CF3-chromenes and CF3-alkenes. To a solution of
propargylic alcohol (0.25 mmol) in HFIP (125 μL), aryl nucleophile was added (0.75 mmol) and
TfOH (2.2 μL, 10 mol%). The reaction was stirred at 50 oC for 16 h. The crude reaction mixture
was directly transferred for silica gel chromatography.
Characterization data for chromenes.
4-Mesityl-2-phenyl-2-(trifluoromethyl)-2H-chromene (4a) was prepared according to
general procedure E from 2-(4,4,4-trifluoro-3-hydroxy-3-phenylbut-1-yn-1-yl)phenol
(73 mg, 0.25 mmol) and mesitylene (105 μL, 0.750 mmol), with 2.2 μL (0.025 mmol)
of triflic acid, in 0.125 mL of HFIP (16 h, 50 °C). Purification by flash column
Ph
CF3
O
chromatography over silica (petroleum ether) gave 101 mg (quantitative yield) of white
o
1
solid. Mp: 90–92 C. H NMR (400 MHz, CDCl3): δ (ppm) 7.67 (d, J = 7.5 Hz, 2H), 7.41–7.33
(m, 3H), 7.20 (t, J = 7.7 Hz, 1H), 7.11 (d, J = 8.1 Hz, 1H), 6.94 (d, J = 10.0 Hz, 2H), 6.77 (t, J =
7.5 Hz, 1H), 6.54 (d, J = 7.6 Hz, 1H), 6.01 (s, 1H), 2.33 (s, 3H), 2.13 (s, 3H), 2.00 (s, 3H). 13C{1H}
NMR (100 MHz, CDCl3): δ (ppm) 151.7, 137.9, 137.5, 136.9, 133.2, 130.6, 129.3, 128.7, 128.6,
128.5, 127.1, 125.7, 125.0 (q, J = 284.6 Hz), 122.5, 120.9, 118.3, 116.9, 80.4 (q, J = 30.1 Hz),
21.4, 20.1, 19.9. 19F NMR (376.5 MHz, CDCl3 CF3CO2H, - ext. st.): δ (ppm) –80.3 (s, 3F). HRMS
(APPI+-Orbitrap) m/z: [M–H]+ for C25H20OF3 Calcd 393.1461; Found 393.1460 (–0.1 ppm).
2-Phenyl-4-(2,3,5,6-tetramethylphenyl)-2-(trifluoromethyl)-2H-chromene (4b) was
prepared according to general procedure E from 2-(4,4,4-trifluoro-3-hydroxy-3-
phenylbut-1-yn-1-yl)phenol (73 mg, 0.25 mmol) and durene (102 mg, 0.75 mmol),
with 2.2 μL (0.025 mmol) of triflic acid, in 0.125 mL of HFIP (16 h, 50 °C).
Ph
CF3
O
Purification by flash column chromatography over silica (petroleum ether) gave 88 mg
(86% yield) of white solid. Mp: 158–160 oC. 1H NMR (400 MHz, CDCl3): δ (ppm) 7.66 (d, J =
7.3 Hz, 2H), 7.42–7.33 (m, 3H), 7.22–7.18 (m, 1H), 7.12 (dd, J = 8.1, 0.9 Hz, 1H), 7.01 (s, 1H),
6.77 (td, J = 7.5, 1.1 Hz, 1H), 6.53 (dd, J = 7.6, 1.4 Hz, 1H), 5.99 (s, 1H), 2.26 (s, 3H), 2.24 (s,
3H), 2.05 (s, 3H), 1.89 (s, 3H). 13C{1H} NMR (100 MHz, CDCl3): δ (ppm) 151.6, 139.0, 137.5,
136.2, 134.3, 134.1, 132.8, 132.6, 131.5, 130.5, 129.3, 128.6, 127.2, 126.0, 124.3 (q, J = 284.6
ACS Paragon Plus Environment

Page 29 of 39
The Journal of Organic Chemistry
1
2
3
4
5
6
19
Hz), 122.4, 121.3, 118.0, 116.8, 80.4 (q, J = 30.5 Hz), 20.4, 20.3, 16.8, 16.6. F NMR (376.5
MHz, CDCl3, CF3CO2H - ext. st.): δ (ppm) –80.3 (s, 3F). HRMS (APPI+-Obitrap) m/z: [M]+. Calcd
for C26H23OF3 408.1696; Found 408.1698 (0.6 ppm).
7
8
9
4-(2,3,4,5,6-Pentamethylphenyl)-2-phenyl-2-(trifluoromethyl)-2H-chromene (4c) was
prepared according to general procedure E from 2-(4,4,4-trifluoro-3-hydroxy-3-
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
phenylbut-1-yn-1-yl)phenol (72.5 mg, 0.25 mmol) and pentamethyl-benzene (111 mg,
0.75 mmol), with 2.2 μL (0.025 mmol) of triflic acid, in 0.125 mL of HFIP (16 h, 50
°C). Purification by flash column chromatography over silica (petroleum ether) gave
Ph
O
CF3
132 mg (quantitative yield) of white solid. Mp: 92–94 oC. 1H NMR (400 MHz, CDCl3): δ (ppm)
7.65 (d, J = 7.3 Hz, 2H), 7.44–7.30 (m, 3H), 7.23–7.17 (m, 1H), 7.12 (dd, J = 8.1, 1.0 Hz, 1H),
6.77 (td, J = 7.5, 1.2 Hz, 1H), 6.56 (dd, J = 7.6, 1.5 Hz, 1H), 6.00 (s, 1H), 2.30 (s, 3H), 2.25 (s,
13
3H), 2.23 (s, 3H), 2.11 (s, 3H), 1.95 (s, 3H). C{1H} NMR (100 MHz, CDCl3): δ (ppm) 151.6,
139.6, 137.5, 136.1, 133.8, 133.2, 132.9, 132.4, 132.2, 130.5, 129.3, 128.6, 127.2, 126.2, 124.4 (q,
J = 284.6 Hz), 122.4, 121.6, 118.1, 116.8, 80.5 (q, J = 30.5 Hz), 18.1, 17.8, 17.2, 16.9, 16.8. 19F
NMR (376.5 MHz, CDCl3, CF3CO2H - ext. st.): δ (ppm) –80.2 (s, 3F). HRMS (APPI+-Orbitrap)
m/z: [M]+. Calcd for C27H25OF3 422.1852; Found 422.1855 (0.7 ppm).
OMe
2-Phenyl-2-(trifluoromethyl)-4-(2,4,6-trimethoxyphenyl)-2H-chromene (4d) was
prepared according to general procedure E from 2-(4,4,4-trifluoro-3-hydroxy-3-
MeO
OMe
a
phenylbut-1-yn-1-yl)phenol (73 mg, 0.25 mmol) and 1,3,5-trimethoxybenzene (116
mg, 0.75 mmol), with 2.2 μL (0.025 mmol) of triflic acid, in 0.125 mL of HFIP (16
50 °C). Purification by flash column chromatography over silica (petroleum
Ph
O
CF3
h,
ether/EtOAc 97:3) gave 47 mg (43% yield) of white solid. Mp: 133–135 oC. 1H NMR (400 MHz,
CDCl3): δ (ppm) 7.74 (d, J = 7.4 Hz, 2H), 7.38-7.32 (m, 3H), 7.11 (t, J = 6.9 Hz, 1H), 7.02 (d, J =
8.1 Hz, 1H), 6.75 (t, J = 7.5 Hz, 1H), 6.64 (d, J = 7.6 Hz, 1H), 6.20 (d, J = 3.4 Hz, 1H), 6.20 (d, J
13
= 7.6 Hz, 1H), 6.13 (s, 1H), 3.87 (s, 3H), 3.69 (s, 3H), 3.67 (s, 3H). C{1H} NMR (100 MHz,
CDCl3): δ (ppm) 161.8, 159.6, 159.4, 151.4, 137.6, 131.7, 129.6, 129.2, 128.2, 127.9, 125.8, 124.7
(q, J = 283.8 Hz), 122.4, 122.0, 120.5, 116.8, 107.3, 91.3, 91.2, 56.3, 56.1, 55.7 (quaternary carbon
19
a displayed a very weak signal). F NMR (376.5 MHz, CDCl3, CF3CO2H - ext. st.): δ (ppm) –
79.9 (s, 3F). HRMS (APPI+-Orbitrap) m/z: [M+H]+ Calcd for C25H22O4F3 443.1465; Found
443.1464 (–0.2 ppm).
4-Mesityl-2-(p-tolyl)-2-(trifluoromethyl)-2H-chromene (4e) was prepared
according to general procedure E from 2-(4,4,4-trifluoro-3-hydroxy-3-(p-tolyl)but-
1-yn-1-yl)phenol (77 mg, 0.25 mmol) and mesitylene (105 μL, 0.75 mmol), with
2.2 μL (0.025 mmol) of triflic acid, in 0.125 mL of HFIP (16 h, 50 °C). Purification
by flash column chromatography over silica (petroleum ether) gave 55 mg (54%
O
CF3
yield) of white solid. 4e was also prepared according to general procedure E from 4-(2-((tert-
butyldimethylsilyl)oxy)phenyl)-1,1,1-trifluoro-2-(p-tolyl)but-3-yn-2-ol (105 mg, 0.25 mmol) and
mesitylene (105 μL, 0.75 mmol), with 2.2 μL (0.025 mmol) of triflic acid, in 0.125 mL of HFIP
(16 h, 50 °C). Purification by flash column chromatography over silica (petroleum ether) gave 290
ACS Paragon Plus Environment