Reaction of trifluoroacetyl acetylenes with β-amino alcohols. Synthesis of enaminoketones and unusual fragmentation

Article abstract of DOI:10.1016/j.jfluchem.2016.08.008

Graphical abstract Highlights Nucleophilic addition of amino alcohols to CF3CO-acetylenes gave enaminoketones. Diastereoselectivity is determined nature of amino alcohol. New type of fragmentation is observed to form amides and acetophenones. Possible reaction mechanism was proposed.

Full text of DOI:10.1016/j.jfluchem.2016.08.008

Journal of Fluorine Chemistry 190 (2016) 61–67
Contents lists available at ScienceDirect
Journal of Fluorine Chemistry
journal homepage: www.elsevier.com/locate/fluor
Reaction of trifluoroacetyl acetylenes with
b
-amino alcohols. Synthesis
of enaminoketones and unusual fragmentation
a,b,
c,
Maria P. Davydova, Dr.a, , Sergey F. Vasilevsky, Prof.
, Valentine G. Nenajdenko, Prof.
*
*
*
a
Voevodsky Institute of Chemical Kinetics and Combustion, Siberian Branch of the Russian Academy of Sciences, 3 Institutskaya str., Novosibirsk 630090,
Russia
b
Department of Natural Sciences, Novosibirsk State University, 630090 Novosibirsk, Russia
c
Department of Chemistry, Moscow State University, Leninskie Gory 1, Moscow 119991, Russia
A R T I C L E I N F O
Article history:
Received 14 July 2016
Received in revised form 4 August 2016
Accepted 5 August 2016
Available online 31 August 2016
1. Introduction
Previously it has been shown that the reaction of acetylenic
ketones with 1,2-diamines [7] and pseudo-ephedrine [9] resulted
in total cleavage of triple bond of starting compounds. Similar
transformation has been also observed in the reaction of
trifluoromethylated halostyrenes with diamines, however trifluor-
omethylated acetylenes have been key intermediates of such
fragmentation [10] (Scheme 1).
This study is devoted to the investigation of Michael addition of
amino alcohols to acetylenic trifluoromethylated ketones as well
as study of new fragmentation in the reaction conditions.
Since the 19th century, the efforts of organic chemists have
mostly been directed towards creation of new carbon-carbon and
carbon-heteroatom bonds. Despite this intense activity, there are
still plenty of molecular frameworks that are extremely challeng-
ing to synthesize, and new and efficient approaches are constantly
needed [1]. Although the approach to create new bonds has clearly
dominated in organic chemistry, carbon-carbon bond cleavage is
now seen as an alternative to the construction of unusual
molecular skeletons (Beckmann fragmentation, the Grob/Eschen-
moser fragmentation) [2]. Over the past few decades, significant
progress has been made in CꢀꢀC bond-cleavage reactions [3] and
they can be categorized into two main approaches: 1) metal-
involved carbon-carbon cleavage [4] and 2) nonmetal-involved
carbon-carbon cleavage [5].
The triple bond of alkynes is known to be one of the strongest
bonds in organic molecules. The cleavage of a triple bond is very
difficult to perform owing to its rather high dissociation energy
(>200 kcal/mol). Despite some rare reports about the cleavage of a
triple CꢀꢀC bond [6] cleavage of this bond without a metal catalyst
remains a very challenging task [7]. On the other hand, new types
of alkyne transformations are very attractive from synthetic point
of view due to alkyne moiety is a recurring functional group in
numerous natural products, bioactive compounds, and organic
materials as well as versatile intermediates in synthesis [8].
2. Results and discussion
In this paper we present the results of reaction of CF3-ynones
with amino alcohols. It should be noted that such ketones [11] have
extremely polarized triple bond due to high EWG nature of CF3CO
fragment. On the other hand carbonyl group of these ketones is
another rather electrophilic center for the attack of various
nucleophiles.
First we studied the synthesis of the corresponding enamino-
ketones by aza-Michael addition of various amino alcohols. It was
demonstrated that this transformation proceeds very cleanly
under room temperature in ethanol to form target adducts in high
yields (Table 1). The reaction is Z-diastereoselective in the case of
amino alcohols having primary amino group, however a mixture of
diastereomers was isolated in the case amino alcohols derived
from secondary amines. These results are totally in agreement with
literature data concerning configuration of trifluoromethylated
enaminoketones. [11]
* Corresponding authors at: Voevodsky Institute of Chemical Kinetics and
Combustion, Siberian Branch of the Russian Academy of Sciences, 3 Institutskaya
str., Novosibirsk 630090, Russia.
E-mail addresses: vasilev@kinetics.nsc.ru (S.F. Vasilevsky),
nenajdenko@org.chem.msu.ru (V.G. Nenajdenko).
http://dx.doi.org/10.1016/j.jfluchem.2016.08.008
0022-1139/ã 2016 Elsevier B.V. All rights reserved.

62
M.P. Davydova et al. / Journal of Fluorine Chemistry 190 (2016) 61–67
Scheme 1. Some examples of metal free fragmentation of acetylenes.
alcohol used and acetophenones were detected in the reaction
mixture.
This type of fragmentation is unknown in the literature. We
Table 1
Synthesis of trifluoromethylated enaminoketones.
N
R
R1
R2
R3
Reaction time, h
Yield, %
believe that influence of trifluoromethyl group is very important in
this case (see proposed mechanism below). Therefore, we decided
to study the reaction more thoroughly to have deeper insight to the
fragmentation process to understand the mechanism of this
reaction. N-Methyl amino ethanol and trifluoroacetylated phenyl-
acetylene were studied as a model system. Variation of solvents,
reagents ratio and temperature shown that the fragmentation
proceeded most efficiently in protic solvent (ethanol) under 80ꢁE
with double excess of the nucleophile. In these particular
conditions we were able to isolate acetophenone and the
corresponding trifluoroacetamide (due to small scale of experi-
ments yields are not very high) (Scheme 2). This type of reaction
was studied also for enaminoketone 3c to demonstrate general
character of the fragmentation. In both reactions the correspond-
ing acetophenones 4 and amide 5 were isolated in good yield.
In addition we decided to perform 19F NMR monitoring of
fragmentation of enaminoketone 3a in ethanol. For this aim
starting material was heated at 80 ꢁE during 12 h. Samples of
reaction mixture were studied using 19F NMR during 12 h. The
results of this study are given on Fig. 1. The reaction proceeds very
cleanly and we observed no formation of any intermediates under
the reaction conditions. This monitoring gave the information
about simultaneous fragmentation of starting ketone and appear-
ance in the reaction mixture of N-methyl amino ethanol derived
trifluoroacetamide 5. At the beginning the reaction is very slow;
however, after some period of time (approximately 30–50 min)
significant acceleration of fragmentation is visible. After comple-
tion of the reaction acetophenone 4a and amide 5 are formed in 1:1
ratio accordingly 1H NMR data.
3a
3b
3c
3d
3e
3f
3g
3h
3i
H
Me
Me
Me
Me
H
Bn
H
H
H
H
H
Me
H
H
Et
H
i-Bu
Ph
Bn
H
H
H
Ph
H
H
H
0.5
1
1
2
8
88
90
93
94
83
69
68
69
92
71
85
Br
OMe
H
H
H
H
H
H
H
5
10
12
20
20
20
CH2OH
H
H
H
H
H
H
3i
3k
H
As a rule the reaction proceeds during 1–2 h, however in the
case of hindered amino alcohols the reaction was much slower
to demand up to 20 h for completion. Unexpectedly, our attempts
to accelerate the transformation by heating (up to 50 ꢁE) or
using excess of amino alcohol (1.5–2 equivalents) resulted in
lower yields and formation of fragmentation products. The
corresponding trifluoroacetamides derived from the amino
Scheme 2. Fragmentation of ynone 1a and enaminoketone 3c.

M.P. Davydova et al. / Journal of Fluorine Chemistry 190 (2016) 61–67
63
0,90
0,80
0,70
0,60
0,50
0,40
0,30
0,20
0,10
0,00
amino enone
amide
2
4
6
8
10 15 20 25 30 40 50 60 90 120 150 180 210 330 560 780
Fig. 1. Monitoring of fragmentation of enone 3a.
condition failed. We believe that hydroxyl group in the structure
facilitates transfer of proton, which is necessary at the step of
fragmentation to eliminate enamine. Finally, hydrolysis of enamine
derived from amino alcohol makes the reaction scheme complete
to give the corresponding trifluoroacetylated amide and aceto-
phenone as products of the fragmentation.
3. Conclusions
Very important question is the mechanism of the reaction. We
proposed a possible scheme of this reaction based on literature
data and our experimental observations. Most probably due to
highly electrophilic nature of trifluoroacetyl fragment the nucleo-
philic attack of second molecule of amino alcohol at the carbonyl
group takes place under the reaction conditions. We believe that
EWG influence of CF3-group is very important in this case to
stabilize such intermediate. We confirmed that the fragmentation
is accelerated by the use of excess of amino alcohol in protic
solvents (ethanol was found solvent of choice). In the case of the
fragmentation of pure enaminoketone first hydrolysis takes place
with trace amounts of water (96% ethanol was used). After
appearance of more nucleophilic amino alcohol in the reaction
mixture the fragmentation is accelerated significantly (Scheme 3).
Quite important moment is also the presence of hydroxyl in the
structure of amino alcohols and enaminoketones 3. Our attempt to
use secondary amine without additional functionality at the same
We investigated the nucleophilic addition of aminoalcohols to
trifluoroacetyl acetylenes. It was found that under room tempera-
ture this reaction provided efficient access to the corresponding
enaminoketones. However, under higher temperature unusual
fragmentation takes place to form the corresponding trifluoroa-
cetylated amides and acetophenones. Possible reaction scheme
was proposed.
4. General information
Column chromatography was performed on SiO2 (Merck 60
(0.063–0.2 mm)). Analytical TLC was performed using Merck silica
gel 60 F254 plates. The IR spectra were recorded using a UR-20
spectrometer. 1H (400.1 MHz), 13C (101.6 MHz), 19F (376.5 MHz)
NMR spectra were recorded on Bruker AVANCE 400 MHz
spectrometer in CDCl3, DMSO-d6 The high-resolution ESI mass
Scheme 3. Possible mechanism of fragmentation.

64
M.P. Davydova et al. / Journal of Fluorine Chemistry 190 (2016) 61–67
spectra were recorded using a Bruker micrOTOF II spectrometer. 2-
Aminoethanol, 2-(methylamino)ethanol, (1R,2S)-2-(methyla-
mino)-1-phenyl-1-propanol, 2-(benzylamino)ethanol, 2-amino-
butan-1-ol, (S)-2-amino-4-methylpentan-1-ol, 3-aminopropane-
1,2-diol, (R)-2-amino-2-phenylethanol, 2-amino-3-phenylpropan-
1-ol were commercially available reactants. Starting acetylenic
ketones 1a–c were prepared and using literature approach [12].
(ESI) (m/z): calcd for C13H13BrF3NNaO2 [M+Na]+ 373.9974, found,
373.9984.
8. (E,Z)-1,1,1-trifluoro-4-((2-hydroxyethyl)(methyl)amino)-4-
(4-methoxyphenyl)but-3-en-2-one (3c)
O
5. General procedure. Synthesis of 3a–k
F3C
A mixture of ynone (1a–c) (0.5 mmol) and amino alcohols (2a–
i) (0.5 mmol) was stirred in ethanol (0.5 mL) at room temperature
for 0.5–20 h. The volatiles were evaporated in vacuo, the residues
were purified on silica (ethyl acetate/hexane) to give 3a–k.
O
N
HO
1
Yield 140 mg (93%), mp 134–135 ꢁC. E-izomer.
(400 MHz, DMSO-d6) 3.16 (s, 3H, NCH3), 3.18–3.19 (m, 2H,
CH2), 3.42–3.43 (m, 2H, CH2), 3.80 (s, 3H, OCH3), 4.78 (br.s, 1H, OH),
5.31 (s,1H, CH), 6.97–6.99 (m, 2H, CHAr), 7.10–7.12 (m, 2H, CHAr).13
NMR (100 MHz, DMSO-d6) 38.7 (NCH3), 54.5 (CH2), 55.1 (OCH3),
= NMR
d
6. (E,Z)-1,1,1-trifluoro-4-((2-hydroxyethyl)(methyl)amino)-4-
phenylbut-3-en-2-one (3a)
C
d
58.6 (CH2), 86.8 (CH), 113.9, 118.0 (q, J 292 Hz, CF3), 126.9, 129.3,
159.6,168.8,172.2. 19F NMR (376 MHz, DMSO-d6) ꢀ75.58. Z-izomer.
1
F3C
=
NMR (400 MHz, DMSO-d6) d 2.83 (s, 3H, NCH3), 3.62 (m, 2H,
CH2), 3.75–3.76 (m, 2H, CH2), 3.80 (s, 3H, OCH3), 5.04 (br.s, 1H, OH),
5.49 (s, 1H, CH), 6.97–6.99 (m, 2H, CHAr), 7.10–7.12 (m, 3H, CHAr).
O
N
13C NMR (100 MHz, DMSO-d6)
d 40.5 (NCH3), 54.3 (CH2), 55.1
HO
(OCH3), 57.2 (CH2), 86.2 (CH), 114.0, 118.0 (q, J 292 Hz, CF3), 127.5,
131.5, 159.8, 168.8, 172.2. 19F NMR (376 MHz, DMSO-d6) ꢀ75.48. IR
1
Yield 120 mg (88%), mp 123–125 ꢁC. E-izomer.
(400 MHz, DMSO-d6) 3.13–3.15 (m, 2H, CH2), 3.18 (s, 3H,
= NMR
(film, cmꢀ1) 1628 (C
O), 3369 (OH). HRMS (ESI) (m/z): calcd for
¼
d
C
14H16F3NNaO3 [M+Na]+ 326.0974, found, 326.0968.
NCH3), 3.40–3.43 (m, 2H, CH2), 4.82 (br.s, 1H, OH), 5.34 (s, 1H,
CH), 7.17-7.19 (m, 2H, CHAr), 7.42–7.43 (m, 3H, CHAr). 13C NMR
9. (E)-1,1,1-trifluoro-4-((1-hydroxy-1-phenylpropan-2-yl)
(methyl)amino)-4-phenylbut-3-en-2-one (3d)
(100 MHz, DMSO-d6)
d 38.7 (NCH3), 54.5 (CH2), 58.6 (CH2), 86.5
(CH), 117.8 (q, J 292 Hz, CF3), 127.6, 128.4, 128.8, 135.0, 168.6, 172.2.
19F NMR (376 MHz, DMSO-d6) ꢀ75.69. Z-izomer.
= NMR
1
(400 MHz, DMSO-d6)
d 2.78 (s, 3H, NCH3), 3.62-3.65 (m, 2H,
CH2), 3.77 (m, 2H, CH2), 5.07 (br.s, 1H, OH), 5.52 (s, 1H, CH), 7.18–
7.19 (m, 2H, CHAr), 7.43–7.44 (m, 3H, CHAr). 13C NMR (100 MHz,
DMSO-d6) d 40.6 (NCH3), 54.9 (CH2), 57.1 (CH2), 85.9 (CH),117.8 (q, J
292 Hz, CF3), 127.2, 128.6, 128.8, 135.7, 168.3, 172.2. 19F NMR
(376 MHz, DMSO-d6) ꢀ75.62. IR (film, cmꢀ1) 1633 (C
¼O), 3406
OH
(OH). HRMS (ESI) (m/z): calcd for C13H14F3NNaO2 [M+Na]+
F3C
N
296.0869, found, 296.0864.
O
7. (E,Z)-4-(4-bromophenyl)-1,1,1-trifluoro-4-((2-hydroxyethyl)
(methyl)amino)but-3-en-2-one (3b)
Yield 170 mg (94%), mp 165–168 ꢁC. 1
1.16 (d, 3 , J 6.65 Hz, CH3), 3.12 (s, 3
E=), 5.20 (s, 1H, CH), 5.65 (d, 1H, J 4.70 Hz, CH), 6.38 (d, 1
7.43 Hz, ?=), 7.01 (d, 2H, J 6.26 Hz, E=Ar), 7.10–7.11 (m, 1H, E=Ar),
7.27–7.41 (m, 7H, E=Ar). 13C NMR (100 MHz, DMSO-d6)
13.7
(CH3), 33.8 (NCH3), 60.8, 73.8, 86.3, 117.6 (q, J 293 Hz, CF3), 126.1,
=
NMR (400 MHz, DMSO-
, NCH3), 4.61–4.64 (m,
, J
d6)
d
,
=
=
1
=
=
Br
F3C
d
O
N
126.4, 127.4, 127.9, 128.3, 128.5, 128.7, 134.9, 142.8, 168.2, 172.4. 19
F
NMR (376 MHz, DMSO-d6) ꢀ75.71. IR (film, cmꢀ1) 1624 (C
¼
O),
HO
3428 (OH). HRMS (ESI) (m/z): calcd for C20H20F3NNaO2 [M + Na]+
1
Yield 160 mg (90%), mp 153–155 ꢁC. E-izomer.
(400 MHz, DMSO-d6) 3.14–3.15 (m, 2H, CH2), 3.17 (s, 3H,
= NMR
386.1338, found, 386.1335.
d
NCH3), 3.42-3.43 (m, 2H, CH2), 4.81 (br.s, 1H, OH), 5.34 (s, 1H,
10. (Z)-1,1,1-trifluoro-4-(2-hydroxyethylamino)-4-phenylbut-3-
en-2-one (3e)
CH), 7.13-7.15 (d, 2H, J 8.22 Hz, CHAr), 7.62–7.64 (d, 2H, J 8.22 Hz,
CHAr). 13C NMR (100 MHz, DMSO-d6)
d 38.7 (NCH3), 54.6 (CH2),
58.4 (CH2), 86.6 (CH), 117.7 (q, J 292 Hz, CF3), 130.0, 131.5, 134.3,
1
167.4, 172.4. 19F NMR (376 MHz, DMSO-d6) ꢀ75.67. Z-izomer.
=
NMR (400 MHz, DMSO-d6)
d 2.80 (s, 3H, NCH3), 3.62-3.64 (m, 2H,
CH2), 3.75 (m, 2H, CH2), 5.06 (br.s, 1H, OH), 5.53 (s, 1H, CH), 7.15–
F3C
7.18 (m, 2H, CHAr), 7.64–7.67 (m, 3H, CHAr). 13C NMR (100 MHz,
O
HN
HO
DMSO-d6) d 40.7 (NCH3), 55.0 (CH2), 57.1 (CH2), 86.1 (CH),117.7 (q, J
292 Hz, CF3), 129.5, 131.8, 135.0, 167.4, 172.4. 19F NMR (376 MHz,
DMSO-d6) ꢀ75.61. IR (film, cmꢀ1) 1630 (C
¼O), 3390 (OH). HRMS

M.P. Davydova et al. / Journal of Fluorine Chemistry 190 (2016) 61–67
65
Yield 100 mg (83%), yellow oil. 1
3.34-3.35 (m, 2H, CH2), 3.50–3.54 (m, 2
4 Hz, OH), 5.30 (s, 1 E=), 7.50–7.53 (m, 5H, E=Ar), 11.25 (br.s, 1H,
). 13C NMR (100 MHz, DMSO-d6)
47.5 (CH2), 59.6 (CH), 88.9
=
NMR (400 MHz, DMSO-d6)
d
13. (Z)-4-(2,3-dihydroxypropylamino)-1,1,1-trifluoro-4-
phenylbut-3-en-2-one (3h)
=, CH2), 5.07–5.09 (t, 1H J
=,
N
=
d
(CH), 117.5 (q, J 278 Hz, CF3), 127.6, 128.8, 130.5, 133.5, 170.5, 173.3.
19F NMR (376 MHz, DMSO-d6) ꢀ75.47. IR (film, cmꢀ1) 1608 (C
¼O),
F3C
3411 (OH). HRMS (ESI) (m/z): calcd for C12H12F3NNaO2 [M+Na]+
282.0718, found, 382.0724.
O
HN
HO
11. (E,Z)-4-(benzyl(2-hydroxyethyl)amino)-1,1,1-trifluoro-4-
phenylbut-3-en-2-one (3f)
OH
Yield 100 mg (69%), mp 102–105 ꢁC. 1
3.19–3.29 (m, 2
CH2), 4.71 (br.s, 1 , OH), 5.27–5.28 (m, 1
7.52–7.54 (m, 5H, E=Ar), 11.30 (br.s, 1H, N
DMSO-d6) 48.3 (CH2), 63.2 (CH2), 69.6 (CH), 88.9 (CH), 117.7 (q, J
=
NMR (400 MHz, DMSO-
d6)
d
=
, CH2), 3.36–3.37 (m, 1H), 3.42–3.46 (m, 2H,
, OH), 5.31 (s, 1H, CH),
). 13C NMR (100 MHz,
=
=
F3C
=
O
N
d
OH
288 Hz, CF3), 127.6, 128.8, 130.5, 133.5, 170.5, 173.2. 19F NMR
(376 MHz, DMSO-d6) ꢀ75.40. IR (film, cmꢀ1) 1604 (C
¼
O), 3403
(OH). HRMS (ESI) (m/z): calcd for C13H14F3NnaO3 [M+Na]+
1
Yield 120 mg (69%), mp 123–125 ꢁC. E-izomer.
(400 MHz, DMSO-d6) 3.22–3.24 (m, 2H, CH2), 3.43–3.47 (m,
2H, CH2), 4.86–4.87 (m, 1H, OH), 4.89 (br.s, 2H, CH2), 5.39 (s, 1H,
CH), 7.11–7.47 (m, 10H, CHAr). 13C NMR (100 MHz, DMSO-d6)
53.9
= NMR
312.0818, found, 312.0815.
d
14. (Z)-1,1,1-trifluoro-4-(1-hydroxy-4-methylpentan-2-
ylamino)-4-phenylbut-3-en-2-one (3i)
d
(CH2), 54.1 (CH2), 59.4 (CH2), 88.7 (CH), 118.3 (q, J 293 Hz, CF3),
126.9, 127.4, 127.9, 128.9, 129.1, 129.2, 135.5, 135.9, 168.6, 172.9. 19
F
1
NMR (376 MHz, DMSO-d6) ꢀ76.09. Z-izomer.
DMSO-d6)
(br.s, 2H, CH2), 5.08–5.11 (m, 1H, OH), 5.66 (s, 1H, CH), 7.11–7.47 (m,
10H, CHAr). 13C NMR (100 MHz, DMSO-d6)
51.8 (CH2), 53.7 (CH2),
= NMR (400 MHz,
3.54–3.57 (m, 2H, CH2), 3.70–3.74 (m, 2H, CH2), 4.38
d
F3C
O
HN
d
OH
56.8 (CH2), 86.7 (CH), 118.1 (q, J 293 Hz, CF3), 127.6, 127.7, 127.9,
129.0, 129.1, 129.2, 135.6, 136.7, 168.8, 172.9. 19F NMR (376 MHz,
DMSO-d6) ꢀ75.76. IR (film, cmꢀ1) 1631 (C
¼
O), 3385 (OH). HRMS
Yield 145 mg (92%), mp 80–82 ꢁC. 1
0.53 (d, 3 , J 6.26 Hz, CH3), 0.71 (d, 3
(m, 2H, CH2), 1.41–1.46 (m, 1 , CH), 3.47–3.49 (m, 1
3.55 (m, 2H, CH2), 5.19-5.21 (t, 1 , J 4.30 Hz, O ), 5.27 (s, 1H, CH),
7.50–7.54 (m, 5H, E=Ar), 11.11 (d, 1H, J 9.39 Hz, N
). 13C NMR
(100 MHz, DMSO-d6) 21.7 (CH3), 22.6 (CH3), 24.0 (CH), 41.1 (CH2),
=
NMR (400 MHz, DMSO-d6)
(ESI) (m/z): calcd for C19H18F3NNaO2 [M+Na]+ 372.1182, found,
d
=
=
, J 6.26 Hz, CH3), 1.33–1.37
, CH), 3.52–
372.1176.
=
=
=
=
12. (Z)-1,1,1-trifluoro-4-(1-hydroxybutan-2-ylamino)-4-
phenylbut-3-en-2-one (3g)
=
d
55.2 (CH2), 63.4 (CH), 88.9 (CH),117.4 (q, J 287 Hz, CF3),127.6,128.8,
130.4, 133.6, 170.6, 173.4. 19F NMR (376 MHz, DMSO-d6) ꢀ75.45. IR
(film, cmꢀ1) 1608 (C
O), 3434 (OH). HRMS (ESI) (m/z): calcd for
C
¼
F3C
16H20F3NNaO2 [M + Na]+ 338.1338, found, 338.1338.
O
HN
OH
15. (Z)-1,1,1-trifluoro-4-(2-hydroxy-1-phenylethylamino)-4-
phenylbut-3-en-2-one (3j)
Yield 110 mg (68%), mp 78–80 ꢁC (benzene). 1
=
NMR (400 MHz,
, CH3), 1.44–1.57 (m, 2H, CH2), 3.48–
E=), 5.29 (s, 1H, CH), 7.50 (m, 5H,
). 13C NMR (100 MHz, DMSO-d6)
DMSO-d6)
3.49 (m, 2
E=Ar), 11.15 (d, 1H, J 9.00 Hz, N
d
=
0.73–0.76 (m, 3
, CH2), 5.16 (s, 1=,
=
=
d
F3C
10.0 (CH3), 24.8 (CH2), 58.4 (CH2), 62.7 (CH), 89.0 (CH), 117.5 (q, J
288 Hz, CF3), 127.5, 128.8, 130.3, 133.7, 170.9, 173.7. 19F NMR
O
HN
(376 MHz, DMSO-d6) ꢀ75.45. IR (film, cmꢀ1) 1602 (C
¼O), 3419
OH
(OH). HRMS (ESI) (m/z): calcd for C14H16F3NNaO2 [M+Na]+
310.1025, found, 310.1024.
Yield 120 mg (71%), yellow oil. 1
3.65–3.77 (m, 2
), 5.38 (s, 1H, CH), 7.17 (d, 2H, J 7.04 Hz, CHAr), 7.26–7.29 (m, 1H,
CHAr), 7.31–7.36 (m, 4H, E=Ar), 7.43–7.47 (m, 2H, E=Ar), 7.50–7.53
(m, 1H, E=Ar), 11.74 (d, 1H, J 9.39 Hz, N
). 13C NMR (100 MHz,
DMSO-d6) 60.5 (CH2), 64.9 (CH), 89.6 (CH),117.5 (q, J 288 Hz, CF3),
=
NMR (400 MHz, DMSO-d6) d
, CH2), 4.67–4.72 (m, 1=, CH), 5.37–5.40 (m, 1=,
=
O=
=
d
126.4, 127.3, 127.6, 128.7, 128.8, 130.6, 133.4, 139.2, 170.5, 174.4. 19
F
O),
NMR (376 MHz, DMSO-d6) ꢀ75.44. IR (film, cmꢀ1) 1607 (C
¼

66
M.P. Davydova et al. / Journal of Fluorine Chemistry 190 (2016) 61–67
3401 (OH). HRMS (ESI) (m/z): calcd for C18H16F3NNaO2 [M+Na]+
Acknowledgments
358.1025, found, 358.1023.
This work was supported by Russian Science Foundation (grant
no. 14-13-00083 for V. Nenajdenko (synthesis of starting
compounds, mechanistic experiments and discussion), other part
of this study was supported by Russian Foundation for Basic
Research for M. Davydova (grant no. 16-03-00589), grant of the
Ministry of Education and Science of the Russian Federation for S.
Vasilevsky and M. Davydova (2014–2016).
16. (Z)-1,1,1-trifluoro-4-(1-hydroxy-3-phenylpropan-2-
ylamino)-4-phenylbut-3-en-2-one (3k)
F3C
O
HN
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M.P. Davydova et al. / Journal of Fluorine Chemistry 190 (2016) 61–67
67
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