Synthesis of 2-trifluoromethyl-2-hydroxy-2H-chromenes via cyclization of (Z)-trifluoromethyl alkenyl triflates and salicylaldehydes

Article abstract of DOI:10.1016/j.jfluchem.2018.05.013

A new and efficient method for the synthesis of 2-trifluoromethyl-2-hydroxy-2H-chromenes was developed via intermolecular cyclization of (Z)-trifluoromethyl alkenyl triflates and salicylaldehydes. A series of 2-trifluoromethyl-2-hydroxy-2H-chromenes with aryl or alkyl groups at 3-position have been obtained in moderate to excellent yields. And a key intermediate, 3-phenyl-4-(pyrrolidin-1-yl)-2-(trifluoromethyl)chroman-2-ol (6), was isolated and fully characterized, which suggests that the elimination of pyrrolidine from this intermediate is the last step during the formation of 2-trifluoromethyl-2-hydroxy-2H-chromenes.

Full text of DOI:10.1016/j.jfluchem.2018.05.013

Accepted Manuscript
Title: Synthesis of
2-trifluoromethyl-2-hydroxy-2H-chromenes via cyclization of
(Z)-trifluoromethyl alkenyl triflates and salicylaldehydes
Authors: Dong Li, Yuhan Zhou, Yilong Zhao, Chunxia Zhang,
Jianzhe Li, Jinfeng Zhao, Jingping Qu
PII:
S0022-1139(18)30161-1
DOI:
Reference:
https://doi.org/10.1016/j.jfluchem.2018.05.013
FLUOR 9176
To appear in:
FLUOR
Received date:
Revised date:
Accepted date:
17-4-2018
26-5-2018
29-5-2018
Please cite this article as: Li D, Zhou Y, Zhao Y, Zhang C, Li J, Zhao J, Qu
J, Synthesis of 2-trifluoromethyl-2-hydroxy-2H-chromenes via cyclization of (Z)-
trifluoromethyl alkenyl triflates and salicylaldehydes, Journal of Fluorine Chemistry
(2018), https://doi.org/10.1016/j.jfluchem.2018.05.013
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Synthesis of 2-trifluoromethyl-2-hydroxy-2H-chromenes via cyclization of
Z)-trifluoromethyl alkenyl triflates and salicylaldehydes
(
Dong Li, Yuhan Zhou*, Yilong Zhao, Chunxia Zhang, Jianzhe Li, Jinfeng Zhao, Jingping Qu
State Key Laboratory of Fine Chemicals, School of Pharmaceutical Science and Technology,
Dalian University of Technology, Dalian 116024, PR China
Graphical Abstract:
A
new
-trifluoromethyl-2-hydroxy-2H-chromenes was developed via intermolecular
cyclization of (Z)-trifluoromethyl alkenyl triflates and salicylaldehydes. A series of
-trifluoromethyl-2-hydroxy-2H-chromenes with aryl or alkyl groups at 3-position
have been obtained in moderate to excellent yields. And a key intermediate,
-phenyl-4-(pyrrolidin-1-yl)-2-(trifluoromethyl)chroman-2-ol (6), was isolated and
fully characterized, which suggests that the elimination of pyrrolidine from this
intermediate is the last step during the formation of
-trifluoromethyl-2-hydroxy-2H-chromenes.
and
efficient
method
for
the
synthesis
of
2
2
3
2
Highlights:




A new approach to 2-trifluoromethyl-2-hydroxy-2H-chromenes with aryl or alkyl groups
at 3-position was described.
(Z)-Trifluoromethyl
alkenyl
triflates
were
applied
on
synthesis
of
2
-trifluoromethyl-2-hydroxy-2H-chromenes.
Salicylaldehydes and (Z)-trifluoromethyl alkenyl triflates reacted smoothly in the
presence of pyrrolidine.
A key intermediate, 3-phenyl-4-(pyrrolidin-1-yl)-2-(trifluoromethyl)chroman-2-ol, was
isolated and fully characterized.

Abstract
A
new
and
efficient
method
for
the
synthesis
of
2
-trifluoromethyl-2-hydroxy-2H-chromenes was developed via intermolecular
cyclization of (Z)-trifluoromethyl alkenyl triflates and salicylaldehydes. A series of
-trifluoromethyl-2-hydroxy-2H-chromenes with aryl or alkyl groups at 3-position
have been obtained in moderate to excellent yields. And a key intermediate,
-phenyl-4-(pyrrolidin-1-yl)-2-(trifluoromethyl)chroman-2-ol (6), was isolated and
fully characterized, which suggests that the elimination of pyrrolidine from this
intermediate is the last step during the formation of
-trifluoromethyl-2-hydroxy-2H-chromenes.
2
3
2
Keywords:
H-chromenes
2
trifluoromethyl alkenyl triflates
salicylaldehydes
cyclization
1
. Introduction
-Substituted 2H-chromenes are main structural motifs of many biologically
2
active molecules and natural products (Figure 1) [1]. They are also used as valuable
intermediates in the preparation of numerous heterocyclic compounds, such as
biscarbazole alkaloids murrafoline and 7-diethylamino-4-methyl coumarin [2]. As a
consequence, efficient synthetic approaches to access 2-substituted 2H-chromenes
have attracted continuous interest [3]. In addition, incorporating a trifluoromethyl
group into an organic molecule has been widely accepted as a powerful tool to
discover
-trifluoromethyl-2-hydroxy-2H-chromenes have gained significant interest in recent
years [5].
new
drugs
[4].
So
it’s
not
surprising
that
2
Figure 1 Biologically active molecule and natural product containing 2-substituted
H-chromenes structure
2

The synthesis of 2-trifluoromethyl-2-hydroxy-2H-chromenes is mostly based on
the Knoevenagel condensation of salicylaldehydes with trifluoromethylated
1
,3-dicarbonyl species [6]. However, the use of this approach is limited to 3-carbonyl
derivatives owing to the availability of respective trifluoromethylated 1,3-dicarbonyl
substrates. Besides, 3-carboalkoxy substituted
-trifluoromethyl-2-hydroxy-2H-chromenes can also be obtained through the reaction
of salicylaldehydes with 4,4,4-trifluorobut-2-ynoate [7]. It is worth noting that using
3,3,3-trifluoroprop-1-yn-1-yl)phosphonate as a trifluoromethylated building block,
the phosphoryl group has been introduced into 3-position of
-trifluoromethyl-2-hydroxy-2H-chromenes by Röschenthaler [8]. Thus, the efficient
2
(
2
synthetic approaches to diverse 2-trifluoromethyl-2-hydroxy-2H-chromenes,
especially 3-aryl or alkyl substituted species, are still highly desired.
Recently, our group also focused on the synthesis of fluorine-containing
compounds [9]. To this end, the useful fluorinated building blocks,
(
Z)-trifluoromethyl alkenyl triflates, were prepared and utilized successfully for the
synthesis of various trifluoromethyl derivatives such as diarylethylenes, alkynes,
enynes, benzofurans, allyl azides, and azirines. In this context, we herein extend the
utilization of (Z)-trifluoromethyl alkenyl triflates to the synthesis of
2
-trifluoromethyl-2-hydroxy-2H-chromenes.
2
. Results and discussion
We
Z)-1-phenyl-3,3,3-trifluoroprop-1-en-2-yl trifluoromethanesulfonate (1a) and
salicylaldehyde (2a) in the presence of triethylamine. The desired
began
our
investigation
with
the
reaction
of
(
3
1
-phenyl-2-(trifluoromethyl)-2H-chromen-2-ol (3a) was afforded in 30% yield (Table
, entry 1) with 3,3,3-trifluoro-1-phenylpropyne (4a) as a by-product. The reaction
was further tested with different bases like DBU, K CO3, KHCO3, pyridine, pyrrole,
2
and pyrrolidine (Table 1, entries 2-7). It was found that the reaction using pyrrolidine
gave the best result (85% yield, Table 1, entry 7), which encouraged us to screen other
bases that has a similar structure to pyrrolidine (Table 1, entries 8-9). Finally,
pyrrolidine proved still to be the best choice for this reaction. In addition, the amount
of 1a and pyrrolidine was screened (Table 1, entries 10-15). To our delight, when the
amount of 1a and pyrrolidine was increased to 2.0 equiv, the yield of 3a was
improved to 98% (Table 1, entry 15). To further optimize the synthesis of 3a, several
parameters such as solvent, temperature, and time were also optimized (Table 2).
Switching the solvent to CH CN, DMF, or toluene failed to give higher yield (Table 2,
3
entries 1-3). Then, the reaction temperature and time were altered but resulted in
lower yields (Table 2, entries 4-13). Performing the reaction in air atmosphere

resulted in a slight decrease in yield (Table 2, entry 14). Through the above screening,
the reaction with 2.0 equiv of 1a, and 2.0 equiv of pyrrolidine in EtOH at 65 °C for 8
h under Ar atmosphere was found to give the highest yield of target product 3a (Table
1
, entry 15).
Table 1 Screening of bases.a
Entry
Base
Et N (2.0 eq.)
DBU (2.0 eq.)
CO (2.0 eq.)
KHCO (2.0 eq.)
Conv. 1a /% b
Yield 3a /% b
1
2
3
4
5
6
7
8
9
3
42
30
33
21
K
2
3
36
19
3
64
29
Pyridine (2.0 eq.)
trace
trace
87
trace
trace
85
Pyrrole (2.0 eq.)
Pyrrolidine (2.0 eq.)
Piperidine (2.0 eq.)
Diethylamine (2.0 eq.)
Pyrrolidine (1.0 eq.)
Pyrrolidine (1.2 eq.)
Pyrrolidine (1.5 eq.)
Pyrrolidine (2.5 eq.)
Pyrrolidine (2.0 eq.)
Pyrrolidine (2.0 eq.)
80
76
75
71
1
0
43
42
11
70
67
1
1
1
2
77
73
3
67
63
4c
5d
89
88
98 (95)e
1
99
a
Reaction conditions: A mixture of 1a (0.6 mmol), 2a (0.5 mmol), base (1.0 mmol) in EtOH (2
b
1
mL) was stirred at 65 °C for 8 h under Ar atmosphere. The yield was determined by H NMR
c
d
with dimethyl terephthalate as an internal standard. 0.75 mmol 1a was used. 1.0 mmol 1a was
e
used. Yield of the isolated product.
a
Table 2 Screening of solvents, temperature and time.
Entry
Solvent
CH CN
DMF
Temp./°C
Time/h
Conv. 1a /% b Yield 3a /% b
1
2
3
65
65
8
8
70
73
64
68

3
4
5
6
7
8
9
1
toluene
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
65
65
25
40
50
60
70
65
65
65
65
65
8
8
8
8
8
8
8
4
6
7
9
8
70
99
62
70
88
93
98
65
73
86
100
99
35
98
14
66
88
92
95
63
68
85
95
91
0
11
1
1
2
3
4c
1
a
Reaction conditions: A mixture of 1a (2.0 mmol), 2a (1.0 mmol), pyrrolidine (2.0 mmol) in
b
1
solvent (3 mL) was stirred under Ar atmosphere. The yield was determined by H NMR with
c
dimethyl terephthalate as an internal standard. Reaction was performed in air.
The reaction scope in terms of salicylaldehydes and (Z)-trifluoromethyl alkenyl
triflates was next explored under the optimized conditions (Table 3). As expected, this
reaction tolerated a wide range of salicylaldehydes bearing either electron-donating or
electron-withdrawing
-trifluoromethyl-2-hydroxy-2H-chromenes in moderate to excellent yields (3a-3j).
Reaction of salicylaldehyde derivatives containing tert-butyl groups at 3-position and
-position, however, occurred in lower yields as a result of the steric effect (3e). In
addition, reaction of salicylaldehyde derivatives containing a hydroxyl group at
-position gave lower yields due to the effect of hydroxyl group (3i). Likewise, the
groups,
affording
the
desired
2
5
4
reactions of (Z)-phenyl-trifluoromethyl alkenyl triflates bearing electron-withdrawing
groups or electron-donating groups were also proved to be effective to afford desired
products in moderate to excellent yields (3j-3t). Specially, alkyl and thiophenyl
substituted (Z)-trifluoromethyl alkenyl triflates were investigated to proceed smoothly
and gave the corresponding products in good yields (3s and 3t). However, the reaction
of (Z)-1-(2-bromophenyl)-3,3,3-trifluoroprop-1-en-2-yl trifluoromethanesulfonate
gave relatively lower yield because of the steric effect (3l). The structure of
compound 3b was further confirmed by X-ray diffraction (Figure 2).
Table 3 Preparation of 2-trifluoromethyl-2-hydroxy-2H-chromenes.

Reaction conditions: A mixture of 1 (2.0 mmol), 2 (1.0 mmol), pyrrolidine (2.0 mmol) in EtOH (3
mL) was stirred at 65 °C for 8-10 h under Ar atmosphere. Yield of the isolated product.
Figure 2 X-ray crystal structure of 3b.
Some control experiments were conducted to understand the reaction mechanism
(Scheme 1). At first, in consideration of the reaction of salicylaldehydes with alkynyl
esters [7,8,10] and the fact that (Z)-trifluoromethyl alkenyl triflates are easy to form
alkyne through an elimination reaction under basic conditions [9b], the reaction
between 1-bromo-4-(3,3,3-trifluoroprop-1-yn-1-yl)benzene (5) and salicylaldehyde
(
2a) was investigated under the optimal reaction conditions. But the desired product
k was not detected (Scheme 1, a). In addition, when the reaction of 1a and 2a was
carried out at °C, the intermediate 6,
3
0

3
-phenyl-4-(pyrrolidin-1-yl)-2-(trifluoromethyl)chroman-2-ol, was isolated in 51%
yield, which can be transformed into the final product 3a upon heating in the presence
of pyrrolidine (Scheme 1, b). The structure of 6 was further confirmed by X-ray
diffraction (Figure 3). To the best of our knowledge, this is the first example of the
isolation and full characterization of the key intermediate 6 in the reaction of
salicylaldehyde and trifluoromethylated species. And it also suggests that the
elimination of pyrrolidine from intermediate 6 is the last step during the formation of
2
-trifluoromethyl-2-hydroxy-2H-chromenes.
Scheme 1 Investigations of the reaction mechanism.
Figure 3 X-ray crystal structure of intermediate 6
On the basis of the above investigations and previous reports [11], the possible
mechanism is shown in Scheme 2. Presumably, the starting material 2 was condensed
with pyrrolidine to give iminium cation intermediate I. Meanwhile,
(
Z)-trifluoromethyl alkenyl triflates 1 was reacted with pyrrolidine to form enamine
intermediate II. Afterwards nucleophilic addition of intermediate II to electrophilic
carbon atom of I occurs, that lead to formation of compound III. Then III has two
possible ways to convert to intermediate V. One way was that hydrolysis of iminium
moiety to carbonyl group took place in the presence of water and gave intermediate
IV, then intramolecular cyclization of intermediate IV furnished intermediate V. The

other was ring closure in III to give intermediate IV’ and subsequent hydrolysis of the
aminal to form intermediate V. Finally, intermediate V underwent an elimination
process to generate product 3 and release another pyrrolidine. The hemiketal structure
in intermediate V and products 3 were stabled by CF group.
3
Scheme 2 Possible mechanism for preparation of products 3.
3
. Conclusions
In conclusion,
an
efficient
method
to
afford
novel
2
3
-trifluoromethyl-2-hydroxy-2H-chromenes containing aryl or alkyl groups at
-position was developed. Salicylaldehydes and (Z)-trifluoromethyl alkenyl triflates
reacted smoothly to afford corresponding 2-trifluoromethyl-2-hydroxy-2H-chromenes
promoted by pyrrolidine. The functional group, such as fluorine, chlorine, bromine,

alkyl, alkoxy, and trifluoromethyl, were all tolerated well, and the desired products
were obtained in moderate to excellent yields. key intermediate,
-phenyl-4-(pyrrolidin-1-yl)-2-(trifluoromethyl)chroman-2-ol (6), was isolated and
A
3
fully characterized, which suggests that the elimination of pyrrolidine from 6 is the
last step during the formation of 2-trifluoromethyl-2-hydroxy-2H-chromenes.
4
. Experimental
4
.1. General information
Unless otherwise noted, all reactions were performed under an Ar atmosphere in
glassware with magnetic stirring. NaH (60% in mineral oil) was washed with dry
n-hexane to remove mineral oil prior to use. Other reagents and solvents were
purchased from commercial sources and used without further purification. Column
chromatography was performed on silica gel (200–300 mesh) using petroleum
1
13
ether/ethyl acetate as an eluent. All H NMR (400 MHz), C NMR (101 MHz) and
19F NMR (377 MHz or 470 MHz) were recorded on Bruker AVANCE II-400 or
Bruker AVANCE III-500 spectrometer with chemical shifts reported as ppm (in
CDCl
3
, CD
3
OD or CD CN with TMS as an internal standard). HRMS (ESI) were
3
recorded on a Micromass GCT spectrometer. X-ray analysis was performed on a
Bruker SMART APEX CCD diffractometer.
4
.2. General procedure for the preparation of (Z)-trifluoromethyl alkenyl triflates 1.
Z)-Trifluoromethyl alkenyl triflates 1 were prepared according to our previous
(
works [9b]. To a suspension of NaH (480 mg, 20.0 mmol) in MTBE (10 mL) was
added ethyl trifluoroacetate (2.4 mL, 20.0 mmol) at room temperature under an Ar
atmosphere. After 1 min of stirring, enolizable ketone (10.0 mmol) was added, and
the mixture was refluxed for 6-12 h. After the reaction was complete (monitored by
TLC or GC analyses), the reaction solution was cooled to 0 °C. Tf
mmol) was added slowly into the reaction mixture. After the reaction was complete
monitored by TLC or GC analyses), the reaction was quenched with ice-water. The
aqueous layer was separated and extracted with EtOAc. The combined organic
extracts were washed with brine, dried over MgSO , and the solvent was removed
2
O (2.86 mL, 20.0
(
4
under reduced pressure. The crude product was purified by column chromatography
on silica gel (petroleum ether as the eluent) to afford the products 1.
(
(
Z)-3,3,3-Trifluoro-1-(4-methoxyphenyl)prop-1-en-2-yl
1j)
trifluoromethanesulfonate
1
) δ 7.58 (d, 3JHH
=
Colorless liquid; yield 72% (2.52 g); H NMR (400 MHz, CDCl
3
.7 Hz, 2H), 7.03 (s, 1H), 6.96 (d, 3JHH = 8.7 Hz, 2H), 3.85 (s, 3H). C NMR (101
13
8

MHz, CDCl
3
) δ 161.8, 132.0, 130.5 (q, 2JCF = 38.3 Hz), 127.6 (q, 3JCF = 7.0 Hz),
20.9, 119.4 (q, 1JCF = 273.7 Hz), 118.0 (q, 1JCF = 322.2 Hz), 114.6, 55.4. F NMR
19
1
(
470 MHz, CDCl
) δ -68.6 (q, 6JFF = 4.7 Hz, 3F), -72.7 (q, 6JFF = 4.7 Hz, 3F). IR (KBr,
3
-1
cm ) v = 1675, 1608, 1516, 1429, 1265, 1023, 886, 831, 681, 604. HRMS (ESI) m/z:
–
calcd for C11
H
7
F
6
O
4
S [M – H] 348.9969, found: 348.9967.
(
Z)-3,3,3-Trifluoro-1-(4-fluorophenyl)prop-1-en-2-yl trifluoromethanesulfonate (1o)
1
Colorless liquid; yield 78% (2.64 g); H NMR (400 MHz, CDCl
3
) δ 7.65 – 7.58 (m,
H), 7.20 – 7.12 (m, 2H), 7.10 (s, 1H). C NMR (101 MHz, CDCl
) δ 164.0 (d, 1JCF
253.7 Hz), 132.1 (d, 3JCF = 8.8 Hz), 126.9 (q, 3JCF = 3.6 Hz), 124.7 (d, 4JCF = 3.5
1
3
2
3
=
Hz), 123.1 (q, 2JCF = 14.4 Hz), 119.1 (q, 1JCF = 273.7 Hz), 118.2 (q, 1JCF = 322.2 Hz),
16.5 (d, 2JCF = 24.2 Hz). F NMR (470 MHz, CDCl
19
) δ -68.1 – -70.3 (m, 3F), -71.5
1
–
1
3
3
-1
-77.6 (m, 3F), -107.1 – -107.4 (m, 1F). IR (KBr, cm ) v = 1682, 1605, 1514, 1432,
241, 1027, 887, 834, 682, 605. HRMS (ESI) m/z: calcd for C10
H
4
F
7
O
S [M – H]–
3
36.9769, found: 336.9767.
(
Z)-3,3,3-Trifluoro-1-[4-(trifluoromethyl)phenyl]prop-1-en-2-yl
trifluoromethanesulfonate (1p)
1
Colorless liquid; yield 74% (2.87 g); H NMR (400 MHz, CDCl
3
) δ 7.71 (m, 4H),
) δ 134.0 (q, 2JCF = 38.9 Hz), 132.7 (q, 2JCF
33.2 Hz), 132.1, 130.0, 126.6 (q, 3JCF = 3.5 Hz), 126.1 (q, 2JCF = 18.9 Hz), 123.5 (q,
1
3
7
.18 (s, 1H). C NMR (101 MHz, CDCl
3
=
1JCF = 272.7 Hz), 118.9 (q, 1JCF = 274.7 Hz), 118.2, (q, 1JCF = 322.2 Hz). F NMR
19
(470 MHz, CDCl
3
) δ -63.3 – -63.5 (m, 3F), -69.6 (q, 6JFF = 4.7 Hz, 3F), -72.8 (q, 6JFF
-1
=
4.7 Hz, 3F). IR (KBr, cm ) v = 1434, 1326, 1284, 1070, 1029, 886, 834, 682, 603.
–
HRMS (ESI) m/z: calcd for C11
H
4
F
9
O S [M – H] 386.9737, found: 386.9733.
3
(
Z)-1,1,1-Trifluoroundec-2-en-2-yl trifluoromethanesulfonate (1s)
1
) δ 6.34 (t, 3JHH = 7.7
Colorless liquid; yield 74% (2.63 g); H NMR (400 MHz, CDCl
3
Hz, 1H), 2.39 – 2.28 (m, 2H), 1.57 – 1.45 (m, 2H), 1.38 – 1.22 (m, 10H), 0.93 – 0.84
1
3
) δ 133.9 (q, 2JCF = 39.1 Hz), 131.3 (q, 3JCF = 3.1
(
m, 3H). C NMR (101 MHz, CDCl
3
Hz), 118.9 (q, 1JCF = 273.7 Hz), 118.1 (q, 1JCF = 322.2 Hz), 31.7, 29.1, 29.0, 27.7,
1
9
2
3
6
6.0, 22.6, 14.0. F NMR (470 MHz, CDCl
) δ -70.1 (s, 3F), -73.2 (q, 6JFF = 4.7 Hz,
3
-1
F). IR (KBr, cm ) v = 2931, 2860, 1695, 1427, 1330, 1221, 1137, 1010, 882, 753,
–
08. HRMS (ESI) m/z: calcd for C12
H
17
F
6
O
3
S [M – H] 355.0803, found: 355.0800.
(
Z)-3,3,3-Trifluoro-1-(thiophen-2-yl)prop-1-en-2-yl trifluoromethanesulfonate (1t)
1
) δ 7.63 (d, 3JHH
=
Colorless liquid; yield 70% (2.28 g); H NMR (400 MHz, CDCl
3
.0 Hz, 1H), 7.56 (d, 3JHH = 3.6 Hz, 1H), 7.24 (s, 1H), 7.18 – 7.14 (m, 1H). C NMR
13
5
(
101 MHz, CDCl
) δ 133.7, 131.8, 130.3, 129.7 (q, 2JCF = 39.0 Hz), 128.1, 121.5 (q,
3

3JCF = 3.9 Hz), 119.5 (q, 1JCF = 273.7 Hz), 118.4 (q, 1JCF = 322.2 Hz). F NMR (470
19
MHz, CDCl
3
) δ -67.7 (q, 6JFF = 4.7 Hz, 3F), -71.9 (q, 6JFF = 4.7 Hz, 3F). IR (KBr,
-1
cm ) v = 1671, 1432, 1134, 1019, 885, 805, 658, 609. HRMS (ESI) m/z: calcd for
–
C
8
H
3
F
6
O
3
S
2
[M – H] 324.9428, found: 324.9426.
4
2
.3.
General
procedure
for
the
preparation
of
-trifluoromethyl-2-hydroxy-2H-chromenes 3.
To a solution of (Z)-trifluoromethyl alkenyl triflates 1 (2.0 mmol) in EtOH (3 mL)
was added salicylaldehydes (1.0 mmol) at room temperature under an Ar atmosphere.
Then pyrrolidine (2.0 mmol) was added, and the mixture was stirred at 65 °C for 8-10
h. After the reaction was complete (monitored by TLC), solvent was removed under
reduced pressure. The crude product was purified by column chromatography on
silica gel (petroleum ether/EtOAc =30:1 as the eluent) to afford the product 3.
3
-Phenyl-2-trifluoromethyl-2H-chromen-2-ol (3a)
1
) δ 7.51 (d, 3JHH
Light yellow liquid; yield 95% (277 mg); H NMR (400 MHz, CDCl
3
=
2.5 Hz, 2H), 7.34 – 7.33 (m, 3H), 7.27 – 7.22 (m, 1H), 7.15 (dd, 3JHH = 7.8, 1.4 Hz,
H), 7.00 (dd, 3JHH = 7.2, 4.0 Hz, 2H), 6.76 (s, 1H), 3.47 (br s, 1H). C NMR (101
13
1
MHz, CDCl
3
) δ 149.3, 136.7, 130.3, 129.2, 129.1, 128.3, 128.1, 127.4, 122.7, 122.2 (q,
1JCF = 290.9 Hz), 119.1, 115.9, 96.4 (q, 2JCF = 33.3 Hz). F NMR (377 MHz, CDCl
19
)
3
-1
δ -81.4. IR (KBr, cm ) v = 3486, 1491, 1458, 1235, 1194, 1116, 1055, 937, 764, 700.
–
HRMS (ESI) m/z: calcd for C16
H
10
F
3
O
2
[M – H] 291.0633, found: 291.0641.
7
-Methoxy-3-phenyl-2-trifluoromethyl-2H-chromen-2-ol (3b)
Light yellow solid; mp. 142 – 143 °C (crystallized in CH
2
Cl /petroleum ether); yield
2
1
) δ 7.51 (dd, 3JHH = 6.4, 2.8 Hz, 2H), 7.36
9
4% (303 mg); H NMR (400 MHz, CDCl
3
–
7.28 (m, 3H), 7.08 – 6.99 (m, 1H), 6.76 (s, 1H), 6.60 – 6.53 (m, 2H), 3.80 (s, 3H).
) δ 161.4, 150.6, 136.9, 129.0, 128.7, 128.2, 128.0, 126.3,
22.2 (q, 1JCF = 289.9 Hz), 112.6, 109.1, 101.4, 96.6 (q, 2JCF = 33.3 Hz), 55.6. 19F
13C NMR (101 MHz, CDCl
3
1
-
1
NMR (377 MHz, CDCl
3
) δ -81.3. IR (KBr, cm ) v = 3423, 1505, 1446, 1203, 1163,
[M – H]–
1
118, 1003, 943, 767, 700. HRMS (ESI) m/z: calcd for C17
H
12
F
3
O
3
3
21.0739, found: 321.0747.
6
-Methyl-3-phenyl-2-trifluoromethyl-2H-chromen-2-ol (3c)
1
Colorless liquid; yield 98% (300 mg); H NMR (400 MHz, CDCl
3
) δ 7.53 – 7.49 (m,
2
1
1
H), 7.36 – 7.32 (m, 3H), 7.08 – 7.03 (m, 1H), 6.96 (s, 1H), 6.91 (d, 3JHH = 8.2 Hz,
13
H), 6.75 (s, 1H), 3.88 (br s, 1H), 2.31 (s, 3H). C NMR (101 MHz, CDCl ) δ 147.2,
3
36.8, 132.1, 130.9, 129.2, 129.0, 128.2, 128.0, 127.7, 122.2 (q, 1JCF = 290.9 Hz),
18.8, 115.6, 96.4 (q, 2JCF = 33.3 Hz), 20.6. F NMR (377 MHz, CDCl
19
) δ -81.2. IR
1
3

-1
(
KBr, cm ) v = 3531, 1607, 1493, 1237, 1190, 1129, 1055, 901, 817, 700. HRMS
–
(
ESI) m/z: calcd for C17
H
12
F
3
O
2
[M – H] 305.0789, found: 305.0798.
2
-Phenyl-3-trifluoromethyl-3H-benzo[f]chromen-3-ol (3d)
1
) δ 7.91 (d, 3JHH
Light yellow liquid; yield 96% (328 mg); H NMR (400 MHz, CDCl
3
=
8.0 Hz, 1H), 7.71 – 7.65 (m, 2H), 7.56 – 7.55 (m, 2H), 7.43 – 7.41 (m, 2H), 7.35 –
.33 (m, 4H), 7.17 (d, 3JHH = 8.0 Hz, 1H), 3.95 (br s, 1H). C NMR (101 MHz,
CDCl ) δ 147.5, 137.0, 130.9, 130.0, 129.6, 129.3, 128.9, 128. 5, 128.2, 128.1, 127.4,
24.8, 124.7, 122.3 (q, 1JCF = 289.9 Hz), 121.2, 117.1, 111.9, 96.3 (q, 2JCF = 33.3 Hz).
13
7
3
1
19F NMR (377 MHz, CDCl
) δ -80.5. IR (KBr, cm ) v = 3464, 1641, 1534, 1293,
242, 1185, 1051, 955, 750, 703. HRMS (ESI) m/z: calcd for C20
[M – H]–
-1
3
1
3
H
12
F O
3 2
41.0789, found: 341.0796.
6
,8-Di-tert-butyl-3-phenyl-2-trifluoromethyl-2H-chromen-2-ol (3e)
1
) δ 7.52 (d, 3JHH
Colorless liquid; yield 57% (231 mg); H NMR (400 MHz, CDCl
3
=
3
.1 Hz, 2H), 7.34 – 7.33 (m, 2H, 2H), 7.07 (d, 3JHH = 2.2 Hz, 1H), 6.80 (d, 3JHH = 2.6
1
3
Hz, 1H), 3.84 (br s, 1H), 1.47 (s, 9H), 1.32 (s, 9H). C NMR (101 MHz, CDCl
3
) δ
1
45.8, 144.8, 136.8, 136.7, 130.2, 129.0, 128.4, 128.1, 128.0, 125.3, 122.5, 122.3 (q,
1JCF = 289.9 Hz), 118.8, 96.2 (q, 2JCF = 33.3 Hz), 34.8, 34.5, 31.5,29.8. F NMR (377
19
-
1
MHz, CDCl
3
) δ -80.0. IR (KBr, cm ) v = 3483, 1433, 1365, 1238, 1188, 1057, 1030,
–
9
4
81, 772, 703. HRMS (ESI) m/z: calcd for C24
03.1898.
H
26
F
3
O
2
[M – H] 403.1885, found:
6
-Chloro-3-phenyl-2-trifluoromethyl-2H-chromen-2-ol (3f)
1
Colorless liquid; yield 94% (307 mg); H NMR (400 MHz, CDCl
3
) δ 7.53 – 7.46 (m,
2
H), 7.39 – 7.30 (m, 3H), 7.22 – 7.16 (m, 1H), 7.13 (d, 3JHH = 2.5 Hz, 1H), 6.93 (d,
3JHH = 8.0 Hz, 1H), 6.69 (s, 1H), 3.93 (br s, 1H). C NMR (101 MHz, CDCl
13
3
) δ 147.8,
1
36.1, 130.5, 130.0, 129.0, 128.6, 128.2, 128.0, 127.6, 126.8, 122.0 (q, 1JCF = 289.9
Hz), 120.4, 117.2, 96.3 (q, 2JCF = 33.3 Hz). F NMR (377 MHz, CDCl
) δ -81.2. IR
19
3
-1
(
KBr, cm ) v = 3502, 1485, 1445, 1232, 1190, 1105, 1055, 905, 811, 701. HRMS
–
(
ESI) m/z: calcd for C16
H
9
ClF
3
O
2
[M – H] 325.0243, found: 325.0255.
6
-Bromo-3-phenyl-2-trifluoromethyl-2H-chromen-2-ol (3g)
1
Colorless liquid; yield 91% (337 mg); H NMR (400 MHz, CDCl
3
) δ 7.53 – 7.46 (m,
2
6
1
1
H), 7.36 – 7.32 (m, 4H), 7.27 (d, 3JHH = 2.4 Hz, 1H), 6.87 (d, 3JHH = 8.6 Hz, 1H),
1
3
.68 (s, 1H), 3.67 (br s, 1H). C NMR (101 MHz, CDCl
3
) δ 148.3, 136.1, 132.9,
30.4, 129.8, 129.0, 128.6, 128.2, 127.9, 122.0 (q, 1JCF = 290.9 Hz), 120.9, 117.6,
14.8, 96.5 (q, 2JCF = 33.3 Hz). F NMR (377 MHz, CDCl
) δ -81.2. IR (KBr, cm ) v
19
-1
3

=
3507, 1644, 1483, 1233, 1191, 1100, 1054, 905, 809, 701. HRMS (ESI) m/z: calcd
–
for C16
H
9
BrF
3
O
2
[M – H] 368.9738, found: 368.9751.
6
,8-Dichloro-3-phenyl-2-trifluoromethyl-2H-chromen-2-ol (3h)
1
Colorless liquid; yield 93% (335 mg); H NMR (400 MHz, CDCl
3
) δ 7.52 – 7.50 (m,
2
6
1
3
1
–
H), 7.41 – 7.33 (m, 3H), 7.31 (d, 3JHH = 2.3 Hz, 1H), 7.07 (d, 3JHH = 2.3 Hz, 1H),
1
3
.70 (s, 1H). C NMR (101 MHz, CDCl
3
) δ 144.0, 135.7, 131.3, 130.0, 128.9, 128.8,
28.2, 127.5, 127.4, 125.3, 121.8 (q, 1JCF = 290.9 Hz), 121.8, 121.4, 96.0 (q, 2JCF
=
1
9
-1
3.3 Hz). F NMR (377 MHz, CDCl ) δ -81.4. IR (KBr, cm ) v = 3548, 1600, 1459,
3
248, 1219, 1095, 1018, 901, 854, 705. HRMS (ESI) m/z: calcd for C16
H
8
Cl
2
F
3
2
O [M
–
H] 358.9853, found: 358.9866.
3
-Phenyl-2-trifluoromethyl-2H-chromene-2,7-diol (3i)
1
OD) δ 7.42 (dd, 3JHH
Colorless liquid; yield 60% (185 mg); H NMR (400 MHz, CD
3
=
7.6, 1.7 Hz, 2H), 7.24 – 7.16 (m, 3H), 6.95 (d, 3JHH = 8.1 Hz, 1H), 6.62 (s, 1H), 6.37
1
3
–
6.34 (m, 2H), 4.76 (s, 2H). C NMR (101 MHz, CD OD) δ 159.3, 151.1, 137.8,
3
1
1
28.7, 128.0, 127.9, 127.4, 127.1, 126.7, 122.5 (q, 1JCF = 289.9 Hz), 111.8, 109.3,
02.1, 96.6 (q, 2JCF = 33.3 Hz). F NMR (377 MHz, CD
19
OD) δ -82.0. IR (KBr, cm-1)
3
v = 3318, 1622, 1508, 1211, 1159, 1127, 1094, 905, 838, 764. HRMS (ESI) m/z: calcd
–
for C16
H
10
F
3
O
3
[M – H] 307.0582, found: 307.0592.
7
-Methoxy-3-(4-methoxyphenyl)-2-trifluoromethyl-2H-chromen-2-ol (3j)
1
) δ 7.46 (d, 3JHH
Light yellow liquid; yield 97% (342 mg); H NMR (400 MHz, CDCl
8.6 Hz, 2H), 7.09 – 7.06 (m, 1H), 6.88 (d, 3JHH = 8.6 Hz, 2H), 6.72 (s, 1H), 6.58 –
3
=
1
3
6
1
1
.57 (m, 2H), 3.81 (s, 3H) 3.79 (s, 3H). C NMR (101 MHz, CDCl ) δ 161.3, 159.4,
3
50.6, 130.2, 129.2, 128.0, 125.8, 122.2 (q, 1JCF = 290.9 Hz), 113.5, 112.7, 109.1,
01.3, 96.6 (q, 2JCF = 33.3 Hz), 55.5, 55.3. F NMR (377 MHz, CDCl
19
3
) δ -81.4. IR
-1
(
KBr, cm ) v = 3372, 1620, 1511, 1244, 1178, 1112, 1015, 837, 741, 700. HRMS
–
(
ESI) m/z: calcd for C18
H
14
F
3
O
4
[M – H] 351.0844, found: 351.0854.
3
-(4-Bromophenyl)-2-trifluoromethyl-2H-chromen-2-ol (3k)
1
) δ 7.47 (d, 3JHH
Colorless liquid; yield 96% (355 mg); H NMR (400 MHz, CDCl
3
=
8
1
1
.0 Hz, 2H), 7.40 (d, 3JHH = 8.0 Hz, 2H), 7.29 – 7.25 (m, 1H), 7.18 (dd, 3JHH = 7.4,
1
3
.1 Hz, 1H), 7.04 – 6.98 (m, 2H), 6.77 (s, 1H). C NMR (101 MHz, CDCl ) δ 149.3,
3
35.7, 131.2, 130.6, 130.6, 129.4, 128.0, 127.5, 122.8, 122.6, 122.1 (q, 1JCF = 290.9
Hz), 118.8, 115.8, 96.2 (q, 2JCF = 33.3 Hz). F NMR (377 MHz, CDCl
19
) δ -81.3. IR
3
-1
(
KBr, cm ) v = 3478, 1488, 1457, 1235, 1192, 1105, 1011, 926, 826, 755. HRMS
–
(
ESI) m/z: calcd for C16
H
9
BrF
3
O
2
[M – H] 368.9738, found: 368.9754.
3
-(2-Bromophenyl)-2-trifluoromethyl-2H-chromen-2-ol (3l)

1
Colorless liquid; yield 43% (159 mg); H NMR (400 MHz, CDCl
3
) δ 7.68 – 7.65 (m,
1
7
1
2
H), 7.47 (d, 3JHH = 7.5 Hz, 1H), 7.35 – 7.28 (m, 2H), 7.25 – 7.17 (m, 2H), 7.10 –
1
3
.01 (m, 2H), 6.77 (s, 1H), 4.21 (s, 1H). C NMR (101 MHz, CDCl ) δ 149.6, 137.0,
3
32.8, 132.3, 132.2, 130.8, 129.9, 127.6, 127.1, 127.0, 124.1, 122.8, 122.0 (q, 1JCF
=
89.9 Hz), 118.7, 116.3, 96.0 (q, 2JCF = 33.3 Hz). F NMR (470 MHz, CDCl
19
3
) δ -80.8.
-1
IR (KBr, cm ) v = 3503, 1489, 1458, 1233, 1190, 1066, 1024, 931, 756, 726. HRMS
–
(
ESI) m/z: calcd for C16
H
9
BrF
3
O
2
[M – H] 368.9738, found: 368.9752.
3
-(4-Chlorophenyl)-2-trifluoromethyl-2H-chromen-2-ol (3m)
1
) δ 7.47 (d, 3JHH
Colorless liquid; yield 98% (320 mg); H NMR (400 MHz, CDCl
3
=
8
1
1
2
.0 Hz, 2H), 7.31 (d, 3JHH = 8.0 Hz, 2H), 7.30 – 7.23 (m, 1H), 7.19 (d, 3JHH = 7.4 Hz,
1
3
H), 7.05 – 7.01 (m, 2H), 6.79 (s, 1H), 3.99 (br s, 1H). C NMR (101 MHz, CDCl
3
) δ
49.3, 135.1, 134.4, 130.5, 130.3, 129.4, 128.3, 127.9, 127.5, 122.8, 122.0 (q, 1JCF
=
90.9 Hz), 118.8, 115.8, 96.2 (q, 2JCF = 33.3 Hz). F NMR (377 MHz, CDCl
19
3
) δ -81.4.
-1
IR (KBr, cm ) v = 3505, 1500, 1458, 1225, 1192, 1136, 1060, 830, 772, 741. HRMS
–
(
ESI) m/z: calcd for C16
H
9
ClF
3
O
2
[M – H] 325.0243, found: 325.0255.
3
-(3-Chlorophenyl)-2-trifluoromethyl-2H-chromen-2-ol (3n)
1
Colorless liquid; yield 93% (303 mg); H NMR (400 MHz, CDCl
3
) δ 7.55 (s, 1H),
7
7
.42 (d, 3JHH = 7.5 Hz, 1H), 7.32 (d, 3JHH = 8.1 Hz, 1H), 7.30 – 7.23 (m, 2H), 7.19 –
1
3
.15 (m, 1H), 7.04 – 7.00 (m, 2H), 6.79 (s, 1H), 4.22 (br s, 1H). C NMR (101 MHz,
CDCl
3
) δ 149.3, 138.4, 133.9, 130.7, 129.8, 129.3, 129.1, 128.4, 127.7, 127.6, 127.3,
22.8, 122.1 (q, 1JCF = 290.9 Hz), 118.7, 115.9, 96.4 (q, 2JCF = 33.3 Hz). F NMR
19
1
-1
(
377 MHz, CDCl
058, 893, 787, 755. HRMS (ESI) m/z: calcd for C16
found: 325.0254.
3
) δ -81.4. IR (KBr, cm ) v = 3501, 1594, 1477, 1234, 1191, 1117,
–
1
H
9
ClF
3
O
2
[M – H] 325.0243,
3
-(4-Fluorophenyl)-2-trifluoromethyl-2H-chromen-2-ol (3o)
1
White solid; mp. 93 – 94 °C (petroleum ether/EtOAc); yield 96% (298 mg); H NMR
(
400 MHz, CDCl
.3 Hz, 1H), 7.09 – 7.00 (m, 4H), 6.79 (s, 1H), 3.63 (br s, 1H). C NMR (101 MHz,
3
) δ 7.55 – 7.47 (m, 2H), 7.29 – 7.27 (m, 1H), 7.20 (dd, 3JHH = 7.7,
1
3
1
CDCl
3
) δ 162.8 (d, 1JCF = 248.5 Hz), 149.2, 132.6 (d, 4JCF = 3.0 Hz), 130.8 (d, 3JCF
=
8
.2 Hz), 130.5, 129.3, 127.9, 127.4, 122.8, 122.1 (q, 1JCF = 289.9 Hz), 118.9, 115.8,
15.0 (d, 2JCF = 21.6 Hz), 96.2 (q, 2JCF = 33.3 Hz). F NMR (470 MHz, CDCl
19
) δ
1
3
-1
-
81.0 (s, 3F), -113.6 (s, 1F). IR (KBr, cm ) v = 3508, 1501, 1460, 1236, 1188, 1128,
–
1
056, 928, 835, 758. HRMS (ESI) m/z: calcd for C16
H
9
F
4
O
2
[M – H] 309.0539,
found: 309.0541.
2
-(Trifluoromethyl)-3-[4-(trifluoromethyl)phenyl]-2H-chromen-2-ol (3p)

1
White solid; mp. 67 – 68 °C (petroleum ether/EtOAc); yield 90% (324 mg); H NMR
400 MHz, CDCl
) δ 7.67 (d, 3JHH = 8.2 Hz, 2H), 7.62 (d, 3JHH = 8.2 Hz, 2H), 7.34 –
.30 (m, 1H), 7.23 (d, 3JHH = 8.0 Hz, 1H), 7.08 – 7.04 (m, 2H), 6.85 (s, 1H), 3.73 (br s,
(
3
7
1
1
3
H). C NMR (101 MHz, CDCl ) δ 149.3, 140.3, 130.9, 130.3, 129.4, 127.6, 125.0 (q,
3
3JCF = 3.7 Hz), 124.1 (q, 1JCF = 273.7 Hz), 122.8, 122.0 (q, 1JCF = 289.9 Hz), 118.6,
19
1
3
15.9, 96.2 (q, 2JCF = 33.3 Hz). F NMR (470 MHz, CDCl
3
) δ -62.7 (s, 3F), -81.2 (s,
-1
F). IR (KBr, cm ) v = 3572, 1492, 1460, 1236, 1198, 1128, 1055, 843, 757, 703.
–
HRMS (ESI) m/z: calcd for C17
H
9
F
6
O
2
[M – H] 359.0507, found: 359.0508.
3
-(p-Tolyl)-2-trifluoromethyl-2H-chromen-2-ol (3q)
1
) δ 7.47 (d, 3JHH
Light yellow liquid; yield 97% (297 mg); H NMR (400 MHz, CDCl
3
=
8.1 Hz, 2H), 7.32 – 7.25 (m, 1H), 7.23 – 7.17 (m, 3H), 7.08 – 7.02 (m, 2H), 6.74 (s,
1
3
1
1
H), 2.34 (s, 3H). C NMR (101 MHz, CDCl
3
) δ 149.4, 138.2, 133.8, 130.2, 129.2,
28.9, 128.8, 128.6, 127.3, 122.6, 122.2 (q, 1JCF = 289.9 Hz), 119.2, 115.8, 96.3 (q,
2JCF = 33.3 Hz), 21.2. F NMR (470 MHz, CDCl
19
) δ -80.8. IR (KBr, cm ) v = 3505,
-1
3
1
490, 1458, 1234, 1194, 1116, 1054, 932, 821, 753. HRMS (ESI) m/z: calcd for
–
C
17
H
12
F
3
O [M – H] 305.0789, found: 305.0797.
2
3
-[(1,1'-Biphenyl)-4-yl]-2-trifluoromethyl-2H-chromen-2-ol (3r)
1
Colorless liquid; yield 78% (287 mg); H NMR (400 MHz, CDCl
3
) δ 7.62 – 7.54 (m,
6
H), 7.44 – 7.40 (m, 2H), 7.33 (t, 3JHH = 7.3 Hz, 1H), 7.28 – 7.21 (m, 1H), 7.18 – 7.13
1
3
(
m, 1H), 7.02 – 6.98 (m, 2H), 6.82 (s, 1H), 4.03 (br s, 1H). C NMR (101 MHz,
CDCl ) δ 149.4, 141.0, 140.5, 135.6, 130.4, 129.5, 129.1, 128.9, 128.8, 127.6, 127.5,
27.1, 126.8, 122.7, 122.2 (q, 1JCF = 289.9 Hz), 119.1, 115.8, 96.3 (q, 2JCF = 33.3 Hz).
3
1
19F NMR (377 MHz, CDCl
) δ -81.1. IR (KBr, cm ) v = 3529, 1488, 1458, 1192,
[M –
-1
3
1
115, 1052, 1005, 933, 837, 765, 726. HRMS (ESI) m/z: calcd for C22
H
14
F
3
O
2
–
H] 367.0946, found: 367.0957.
3
-Octyl-2-trifluoromethyl-2H-chromen-2-ol (3s)
1
Light yellow liquid; yield 90% (296 mg); H NMR (400 MHz, CDCl
3
) δ 7.20 – 7.14
(
m, 1H), 7.09 (d, 3JHH = 7.3 Hz, 1H), 6.99 – 6.93 (m, 2H), 6.56 (s, 1H), 3.17 (br s, 1H),
2
.47 – 2.21 (m, 2H), 1.63 – 1.58 (m, 2H), 1.36 – 1.20 (m, 10H), 0.89 (t, 3JHH = 6.4 Hz,
1
3
3
H). C NMR (101 MHz, CDCl ) δ 149.3, 129.8, 129.4, 126.6, 124.9, 122.4, 122.4 (q,
3
1JCF = 290.9 Hz), 119.4, 115.5, 96.5 (q, 2JCF = 33.3 Hz), 31.9, 30.1, 29.5, 29.4, 29.3,
1
9
-1
2
2
–
8.1, 22.7, 14.1. F NMR (377 MHz, CDCl ) δ -82.7. IR (KBr, cm ) v = 3417, 2929,
3
858, 1491, 1459, 1233, 1183, 1046, 753. HRMS (ESI) m/z: calcd for C18
H
22
F
3
2
O [M
–
H] 327.1572, found: 327.1582.
3
-(Thiophen-2-yl)-2-trifluoromethyl-2H-chromen-2-ol (3t)

1
) δ 7.38 (d, 3JHH
Light yellow liquid; yield 84% (250 mg); H NMR (400 MHz, CDCl
3.5 Hz, 1H), 7.26 (d, 3JHH = 5.1 Hz, 1H), 7.23 – 7.19 (m, 1H), 7.14 (d, 3JHH = 6.6
3
=
1
3
Hz, 1H), 7.04 – 6.93 (m, 4H), 3.99 (br s, 1H). C NMR (101 MHz, CDCl
3
) δ 150.3,
1
1
38.0, 130.5, 128.0, 127.7, 127.4, 127.3, 126.1, 122.7, 122.4 (q, 1JCF = 292.9 Hz),
22.0, 119.1, 115.2, 96.6 (q, 2JCF = 33.3 Hz). F NMR (470 MHz, CDCl
) δ -83.2. IR
19
3
-1
(
KBr, cm ) v = 3492, 1488, 1457, 1282, 1191, 1158, 1082, 965, 761, 718. HRMS
–
(
ESI) m/z: calcd for C14
H
8
F
3
O
2
S [M – H] 297.0197, found: 297.0200.
4
.4. Preparation of 3-phenyl-4-(pyrrolidin-1-yl)-2-(trifluoromethyl)chroman-2-ol (6)
To a solution of (Z)-trifluoromethyl alkenyl triflates 1a (2.0 mmol) in EtOH (3
mL) was added salicylaldehyde 2a (1.0 mmol) at 0 °C under an Ar atmosphere. Then
pyrrolidine (2.0 mmol) was added, and the mixture was stirred at 0 °C for 1 h to
precipitate a white solid. After the reaction was complete (monitored by TLC), the
white solid was filtered, washed with cool EtOH, and crystallized in toluene to afford
aimed product.
1
White solid; mp. 127 – 128 °C (toluene); yield 51% (182 mg) H NMR (400 MHz,
CDCl
m, 3H), 3.89 (s, 1H), 3.57 (s, 1H), 3.01 (br s, 2H), 2.55 (s, 2H), 1.86 – 1.77 (m, 4H).
13C NMR (101 MHz, CDCl
) δ 151.6, 135.6, 132.5, 130.8, 128.9, 128.4, 127.8, 121.8
q, 1JCF = 286.8 Hz), 121.5, 118.4, 118.1, 97.3 (q, 2JCF = 32.0 Hz), 65.5, 52.0, 43.7,
3
) δ 11.94 (s, 1H), 7.38 (t, 3JHH = 7.7 Hz, 1H), 7.20 – 7.12 (m, 5H), 7.06 – 6.87
(
3
(
1
9
-1
2
1
3.2. F NMR (470 MHz, CD CN) δ -82.1. IR (KBr, cm ) v = 2982, 2832, 1586,
3
456, 1297, 1219, 1197, 1128, 1097, 1016, 990, 764, 704. HRMS (ESI) m/z: calcd for
+
C
20
H
21
F
3
NO
2
[M + H] 364.1524, found: 364.1522.
4
.5. The X-Ray Crystal Structure Determination.
The crystals of 3b and 6 were obtained by slow evaporation of the solution (3b in
CH
2
Cl and 6 in toluene) at room temperature. The data were obtained on a CCD
2
diffractometer with graphite-monochromated. Mo Kα radiation (λ = 0.71073 Å).
Empirical absorption corrections were performed using the SADABS program [12].
Structures were solved by direct methods and were refined by full-matrix
least-squares based on all data using F2 in Shelx97 [13,14]. All of the non-hydrogen
atoms were refined anisotropically. All of the hydrogen atoms were generated and
refined in ideal positions. CCDC-1832869/1832870 contains the supplementary
crystallographic data, which can be obtained free of charge from The Cambridge
Crystallographic Data Centre via www.ccdc.cam.ac.uk/structures/.
Acknowledgments
The authors gratefully acknowledge the financial support of the National Natural
Science Foundation of China (No. 21376040) and the program for Changjiang

Scholars and Innovative Research Team in University (No. IRT13008). We also thank
Prof. Baomin Wang, Dr. Yuming Song, and Dr. Ying Peng (Dalian University of
Technology, China) for valuable discussions.
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