Zinc promoted asymmetric propargylation of N-(2-chlorotetrafluoroethanesulfin)imines

Article abstract of DOI:10.1016/j.jfluchem.2014.08.008

Zinc promoted asymmetric Barbier-type homopropargylation of aldimines is demonstrated. 2-Chlorotetrafluoroethanesulfinamide was used as the chiral auxiliary and the corresponding homopropargylamines were obtained in good yields with up to 98% diastereosel

Full text of DOI:10.1016/j.jfluchem.2014.08.008

Journal of Fluorine Chemistry 168 (2014) 44–49
Contents lists available at ScienceDirect
Journal of Fluorine Chemistry
journal homepage: www.elsevier.com/locate/fluor
Zinc promoted asymmetric propargylation
of N-(2-chlorotetrafluoroethanesulfin)imines
*
Li-Juan Liu, Jin-Tao Liu
Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road,
Shanghai 200032, China
A R T I C L E I N F O
A B S T R A C T
Article history:
Zinc promoted asymmetric Barbier-type homopropargylation of aldimines is demonstrated. 2-
Chlorotetrafluoroethanesulfinamide was used as the chiral auxiliary and the corresponding
homopropargylamines were obtained in good yields with up to 98% diastereoselectivity under mild
conditions.
Received 22 May 2014
Received in revised form 9 August 2014
Accepted 12 August 2014
Available online 23 August 2014
ß 2014 Elsevier B.V. All rights reserved.
Keywords:
2-Chlorotetrafluoroethanesulfinimine
Homopropargylamine
Chiral auxiliary
Asymmetric synthesis
Fluorine
1. Introduction
however, direct asymmetric addition of propargyl zinc to imines
with both good diastereoselectivities and yields has not been
Homopropargylic amines represent the core of many pharma-
ceuticals [1] and constitute versatile precursors of nitrogen-
containing building blocks [2]. Their racemic synthesis through the
attack of nucleophiles to imines has been well developed [3].
However, only a few methods were reported for the efficient
preparation of enantiomerically enriched homopropargylic amines
[4,5], and their synthesis still remains a challenge. In 2008, the
reaction of enantiomerically pure N-sulfinylimines with Grignard
reagents was reported in the enantioselective synthesis of
dihydroisoindol-4-ols [6]. However, only one example was given
for the propargylic reaction, the addition of 1-propynylmagnesium
bromide to (S)-tert-butanesulfinimine derived from 5-methyl
furfural at ꢀ50 8C, which afforded the corresponding adduct in
70% yield with 95% de. Very recently, Yus and coworkers reported
the Barbier-type reaction of chiral tert-butanesulfinimines with
silylated propargyl bromides promoted by indium under sonica-
tion [7]. Good yields and diastereoselectivities were achieved, but
the diastereoselectivities were poor when zinc was used instead of
indium. It is well known that the Barbier-type synthesis involving
the attack of propargyl zinc to imines is appealing for cheap
materials and mild reaction conditions [2(b),8]. Up to now,
reported.
Herein, we report for the first time the Ti(Oi-Pr)4 and CuCl
catalyzed diastereoselective homopropargylation of 2-chlorote-
trafluoroethanesulfinimines with propargyl zinc.
2. Results and discussion
Recently,
a kind of practical fluorinated chiral auxiliary,
polyfluoroalkanesulfinamide, was developed in our laboratory
[9]. Like the tert-butanesulfinyl induced aminoallylation [10], zinc
mediated one-pot aminoallylation of aldehyde was achieved
successfully using (S)-2-chlorotetrafluoroethanesulfinamide (1)
as the auxiliary (Scheme 1) [11]. The corresponding allylic amines
4 with a configuration of Ss, Sc were obtained in good yields with
high diastereoselectivities. Due to the strong electron-withdraw-
ing effect of fluoroalkanesulfinyl group, the reaction could take
place at lower temperature. In addition, the presence of fluorine
facilitated the detection of the reaction process and the diaster-
eoselectivity by 19F NMR spectrum without working-up of the
reaction mixture.
Inspired by this result, we further tried the aminopropargylation
of aldehydes following the procedure depicted in Scheme 1. In
an initial trial, compound
1 was treated with 1.1 equiv of
4-chlorobenzaldehyde (2a) in the presence of zinc powder
(2.0 equiv) and Ti(Oi-Pr)4 (1.5 equiv) in THF at room temperature.
*
Corresponding author. Tel.:+86 21 54925188.
E-mail address: jtliu@sioc.ac.cn (J.-T. Liu).
http://dx.doi.org/10.1016/j.jfluchem.2014.08.008
0022-1139/ß 2014 Elsevier B.V. All rights reserved.

L.-J. Liu, J.-T. Liu / Journal of Fluorine Chemistry 168 (2014) 44–49
45
Scheme 1. One-pot aminoallylation of aldehydes.
Scheme 2. One-pot aminopropargylation of 2a.
After 1 disappeared, propargyl bromide (5a) was added and the
reaction temperature was raised to 35 8C. Unfortunately, only imine
6a was obtained and no expected homopropargylic amine 7a was
observed in 19F NMR spectrum (Scheme 2). Carrying out the reaction
under reflux still failed to afford 7a.
However, when imine 6a was isolated and treated with 5a
(2.0 equiv) in the presence of 2.0 equiv of zinc and 0.2 equiv of
Ti(Oi-Pr)4 at 35 8C in THF, a small amount of the desired product 7a
was observed in 19F NMR spectrum. Raising the temperature to
50 8C, 7a (Ss, Sc) was obtained in 80% yield with a de of 80% as
shown in 19F NMR spectrum (Table 1, entry 1). Further screening
the reaction conditions showed that the addition of 0.1 equiv of
CuCl could improve the yield of 7a to 90% without any erosion in
diastereoselectivity (entry 2). Additionally, when the reaction was
carried out without Ti(Oi-Pr)4, 7a was not detected and imine 6a
was recovered.
Under the optimized conditions, the scope of imines 6 was
investigated and the results are summarized in Table 1. The
reaction tolerated
a broad range of functional groups and
the electronic effect of substituents has little influence on the
reactivity of imines 6. Halide substituted imines 6c–6g reacted
well with 5a to give the corresponding products 7c–7g in good
yields with high diastereoselectivities (Table 1, entries 4-8). The
use of a bromo substitution allows further modification of products
7. The reactions of electron-rich imines bearing methyl- (entry 9),
phenyl- (entry 10), or methoxy-substitution (entry 12) proceeded
well under the reaction conditions, although a slightly prolonged
reaction time was required. Heteroaryl imines 6l and 6m (entries
13 and 14) reacted smoothly and afforded the corresponding
products in good yields. Good yields were also achieved with
imines derived from aliphatic aldedydes, although the diastereos-
electivities were lower (entries 16–18). For imine 6q, products 7q
Table 1
2-Chlorotetrafluoroethanesulfinyl group induced homopropargylation of imines 6
.
Entry
Imine
R
Time (h)
Product
Isolated yield (%)
de (%)b
1a
2
6a
6a
6b
6c
6d
6e
6f
p-ClC6H4
p-ClC6H4
C6H5
8
8
7a
7a
(80)b
79(90)b
73
80
80
3
10
8
7b
7c
84
4
m-ClC6H4
o-ClC6H4
p-FC6H4
66
76
5
10
9
7d
7e
67
92
6
81
>96
>96
88
7
o-FC6H4
12
14
10
13
7
7f
58
8
6g
6h
6i
p-BrC6H4
p-MeC6H4
p-PhC6H4
p-CF3C6H4
p-MeOC6H4
2-Furyl
7g
7h
7i
61
9
82
>98
>98
88
10
11
12
13
14
15
16
17
18
79
6j
7j
65
6k
6l
11
11
14
10
9
7k
7l
81
>98
>98
72
84
6m
6n
6o
6p
6q
2-Thienyl
t-Bu
7m
6n
7o
7p
7q/7q0
65
–
–
Cyclohexyl
(CH3)2CH
PhCH5CH(E)
72
72
9
74
64
10
67/13
60
a
The reaction was carried out without CuCl.
Yields in brackets and de were determined by 19F NMR spectra.
b

46
L.-J. Liu, J.-T. Liu / Journal of Fluorine Chemistry 168 (2014) 44–49
Scheme 3. The reaction of 6r and 5a.
Scheme 4. Conversion of 7b to 9b.
and 7q0 were isolated as diastereomers (entry 18). In the case of 6n,
the addition reaction did not occur because of the steric hindrance,
and 62% of 6n was recovered after workup of the reaction mixture
(entry 15).
To determine the stereoselectivity of the product, 7b was
subjected to deprotection and re-protection with Tosyl group in
sequence (Scheme 4). As a result, 9b (>98% ee) was obtained in a
total yield of 64%. Comparing the optical rotation of 9b with the
reported value [4(b)] indicated that the configuration of the new
generated chiral center in compound 7 was S.
Taking imine 6a as an example, the scope of substituted
propargylic bromides was investigated. The reactions of 6a
with 5b, 5c or 5d were carried out under the optimal conditions
and the results were summarized in Fig. 1. The expected
As
a control experiment, imine 6r prepared from tert-
butanesulfinamide and aldehyde 2a was treated with 5a under
similar conditions, but no adduct was observed and 6r was all
recovered (Scheme 3). In comparison with the result of entry 2 in
Table 1, it revealed that the electrophilicity of the corresponding
imines was obviously enhanced by the fluoroalkanesulfinyl group.
Fig. 1. The reaction of 6a with substituted propargylic bromides.
Scheme 5. The reaction of 5b under different conditions.

L.-J. Liu, J.-T. Liu / Journal of Fluorine Chemistry 168 (2014) 44–49
47
homopropargylic amine 7s was obtained in 79% yield with a
de of 76% from 5b. For dimethyl substituted propargylic
bromide 5d, the reaction took place at higher temperature
(65 8C) due to the steric hindrance. As a result, the addition
product 7u was obtained with a lower yield (60%) and de (68%).
Surprisingly, the diene product 7t was obtained in 80% yield
with up to 84% de when methyl substituted imine 5c was used as
the substrate.
(d, J = 2.4 Hz, 1H), 2.73–2.78 (m, 2H), 4.77 (dd, J = 12.6, 6.6 Hz, 1H),
5.30 (d, J = 6.6 Hz, 1H), 7.31 (d, J = 9.0 Hz, 2H), 7.35 (d, J = 6.0 Hz,
2H). 19F NMR (CDCl3, 282 MHz)
d
(ppm) ꢀ66.56 (s, 2F), ꢀ114.73 (d,
JFF = 232.7 Hz, 1F), ꢀ120.28 (d, JFF = 232.7 Hz, 1F). 13C NMR (CDCl3,
100 MHz) d (ppm) 28.4, 55.3, 73.0, 78.4, 128.3, 129.2, 134.6, 137.8.
HRMS (ESI) calcd for C12H9Cl2F4NOSNa [M + Na]+ 383.9610, found
383.9629.
It was mentioned in Scheme 2 that this homopropargylic
reaction only applied to isolated imines 6. The one-pot amino-
propargylation of aldehydes using 1 as the auxiliary did not work
like the aminoallylation. The preliminary results indicated that it
might be caused by the water produced during the formation of
imines 6. As shown in Scheme 5, when water (1.0 equiv) was added
to the reaction system of 6a and 5b under the standard conditions
(Eq. (1)), no desired addition product was found and imine 6a
remained unchanged. Instead, propa-1,2-dien-1-ylbenzene (10b)
was isolated in 76% yield. Therefore, 10b should be derived from 5b
under the reaction conditions. The result of control experiment
confirmed that (Eq. (2)): when 5b was subjected to the same
conditions in the absence of 6a, 10b was obtained in 80% yield. This
explains why the one-pot aminopropargylation reaction could not
occur.
4.2.2. (4S,Ss)-N-(2-Chlorotetrafluoroethanesulfinyl)-4-phenylbut-1-
yne-4-amine (7b)
Colorless oil. FT-IR (film) 3311, 2362, 1497, 1263, 906, 803,
701 cmꢀ1
.
1H NMR (CDCl3, 400 MHz)
d
(ppm) 2.09 (t, J = 2.6 Hz,
1H), 2.78–2.81 (m, 2H), 4.77 (dd, J = 12.6, 6.4 Hz, 1H), 5.23 (d,
J = 6.4 Hz, 1H), 7.33–7.40 (m, 5H). 19F NMR (CDCl3, 282 MHz)
(ppm) ꢀ66.97 (s, 2F), ꢀ115.72 (d, JFF = 233.8 Hz, 1F), ꢀ120.70 (d,
JFF = 233.8 Hz, 1F). 13C NMR (CDCl3, 100 MHz)
(ppm) 28.4, 56.5,
72.7, 78.9, 126.9, 129.0, 128.7, 139.2. HRMS (ESI) calcd for
12H10ClF4NOSNa [M + Na]+ 350.0000, found 349.9998;
d
d
C
½ ꢁ
a 2D6
ꢀ44.4 (c 1.0, CHCl3).
4.2.3. (4S,Ss)-N-(2-Chlorotetrafluoroethanesulfinyl)-4-(m-
chlorophenyl)but-1-yne-4-amine (7c)
Colorless oil. FT-IR (film) 3302, 2927, 1598, 1577, 1479, 1434,
1262, 905, 794, 696 cmꢀ1. 1H NMR (CDCl3, 300 MHz)
(ppm) 2.09–
d
3. Conclusions
2.14 (m, 1H), 2.76–2.82 (m, 2H), 4.77 (dd, J = 12.8, 6.3 Hz, 1H), 5.17
(d, J = 6.9 Hz, 1H), 7.27 (dd, J = 2.7, 2.7 Hz, 1H), 7.32–7.34 (m, 2H),
In summary, we have developed an efficient asymmetric
homopropargylation of aldimines induced by 2-chlorotetrafluor-
oethanesulfinyl group. Good yields and excellent de were achieved
for various imines under mild conditions. Further synthetic
application of this reaction and the application of polyfluoroalk-
anesulfinamide in asymmetric synthesis are in progress in our
laboratory.
7.36 (s, 1H). 19F NMR (CDCl3, 282 MHz)
d
(ppm) ꢀ66.35 (s, 2F),
ꢀ114.43 (d, JFF = 233.8 Hz, 1F), ꢀ120.19 (d, JFF = 233.8 Hz, 1F). 13C
NMR (CDCl3, 100 MHz) d (ppm) 28.3, 55.2, 73.0, 78.2, 125.0, 126.1,
127.0, 128.8, 130.2, 134.8. HRMS (ESI) calcd for C12H9Cl2F4NOSNa
[M + Na]+ 383.9610, found 383.9608.
4.2.4. (4S,Ss)-N-(2-Chlorotetrafluoroethanesulfinyl)-4-(o-
chlorophenyl)but-1-yne-4-amine (7d)
4. Experimental
Colorless oil. FT-IR (film) 3307, 2926, 2360, 1574, 1421, 1262,
1018, 903, 797, 751, 552 cmꢀ1. 1H NMR (CDCl3, 300 MHz)
d (ppm)
4.1. General remarks
2.11 (t, J = 2.4 Hz, 1H), 2.80–2.86 (m, 2H), 5.26 (dd, J = 13.2, 5.4 Hz,
1H), 5.39 (d, J = 7.8 Hz, 1H), 7.28–7.50 (m, 4H). 19F NMR (CDCl3,
1H NMR spectra were recorded at 300 or 400 MHz using CDCl3
as the solvent and TMS as the internal standard. The data are
reported as (s = singlet, d = doublet, m = multiplet, coupling
constant in Hz, integration). 19F NMR spectra were recorded at
282 MHz)
d
(ppm) ꢀ66.59 (s, 2F), ꢀ114.62 (d, JFF = 233.8 Hz, 1F),
ꢀ120.95 (d, JFF = 233.8 Hz, 1F). 13C NMR (CDCl3, 100 MHz)
d (ppm)
27.0, 52.2, 73.0, 78.2, 127.3, 128.4, 129.7, 130.1, 132.5, 136.8. HRMS
(ESI) calcd for C12H9Cl2F4NOSNa [M + Na]+ 383.9610, found
383.9607.
282 MHz, chemical shifts (d,
1H-decoupled) are reported in ppm
using CFCl3 as internal standard. 13C NMR spectra were recorded
with 1H-depoupling at 100 MHz and referenced to CDCl3 at
77.16 ppm. Flash chromatography was carried out on handpacked
columns of silica gel (300–400 mesh). THF and CH2Cl2 were freshly
distilled and all other commercially available reagents were used
as received.
4.2.5. (4S,Ss)-N-(2-Chlorotetrafluoroethanesulfinyl)-4-(p-
fluorophenyl)but-1-yne-4-amine (7e)
Colorless oil. FT-IR (film) 3308, 2928, 1606, 1514, 1428, 1263,
1175, 1013, 908, 796, 652 cmꢀ1. 1H NMR (CDCl3, 300 MHz)
d (ppm)
2.10 (d, J = 2.4 Hz, 1H), 2.75–2.79 (m, 2H), 4.76 (dd, J = 12.3, 6.3 Hz,
1H), 5.25 (d, J = 6.3 Hz, 1H), 7.04–7.14 (m, 2H), 7.34–7.38 (m, 2H).
4.2. General procedure for homopropargylation of imines 6
19F NMR (CDCl3, 282 MHz)
d
(ppm) ꢀ66.79 (s, 2F), ꢀ113.02 to
ꢀ113.10 (m, 1F), ꢀ115.28 (d, JFF = 232.7 Hz, 1F), ꢀ120.43 (d,
JFF = 232.7 Hz, 1F). 13C NMR (CDCl3, 100 MHz)
(ppm) 28.4, 55.6,
To a mixture of imine 6 (1.0 mmol), zinc power (2.0 mmol) and
THF (2.0 mL) was added CuCl (0.1 mmol), Ti(Oi-Pr)4 (0.2 mmol)
and 5a (2.0 mmol). The resulting mixture was stirred at 50 8C and
monitored by 19F NMR. After disappearance of 6, the mixture was
cooled to room temperature and diluted with Et2O (10 mL). The
resulting mixture was filtrated through celite and the solid was
washed with Et2O (5 mL). The filtrate was concentrated under
reduced pressure and purified by column chromatography (EA/PE:
1/30), giving product 7.
d
72.9, 78.6, 116.0 (d, J = 21.9 Hz), 128.7 (d, J = 8.0 Hz), 135.1, 162.8
(d, J = 246.5 Hz). HRMS (ESI) calcd for C12H9ClF5NOSNa [M + Na]+
367.9906, found 367.9904.
4.2.6. (4S,Ss)-N-(2-Chlorotetrafluoroethanesulfinyl)-4-(o-
fluorophenyl)but-1-yne-4-amine (7f)
Colorless oil. FT-IR (film) 3310, 2918, 2361, 1618, 1588, 1492,
1459, 1263, 1170, 1012, 909, 801, 759, 655 cmꢀ1. 1H NMR (CDCl3,
300 MHz)
5.02–5.09 (m, 1H), 5.26 (d, J = 8.4 Hz, 1H), 7.06–7.23 (m, 2H),
7.29–7.43 (m, 2H). 19F NMR (CDCl3, 282 MHz)
(ppm) ꢀ66.56
(s, 2F), ꢀ114.85 (d, JFF = 229.6 Hz, 1F), ꢀ117.90 (s, 1F), ꢀ120.41
(d, JFF = 229.6 Hz, 1F). 13C NMR (CDCl3, 100 MHz)
(ppm) 27.7,
d (ppm) 2.08 (t, J = 2.6 Hz, 1H), 2.81–2.89 (m, 2H),
4.2.1. (4S,Ss)-N-(2-Chlorotetrafluoroethanesulfinyl)-4-(p-
chlorophenyl)but-1-yne-4-amine (7a)
d
Colorless oil. FT-IR (film) 3306, 2925, 1599, 1495, 1262, 1176,
908, 797, 650 cmꢀ1
.
1H NMR (CDCl3, 300 MHz)
d
(ppm) 2.09
d

48
L.-J. Liu, J.-T. Liu / Journal of Fluorine Chemistry 168 (2014) 44–49
51.1, 72.7, 78.5, 116.0 (d, J = 21.9 Hz), 124.6 (d, J = 3.7 Hz), 126.7
(d, J = 13.1 Hz), 128.6 (d, J = 3.6 Hz), 130.4 (d, J = 8.7 Hz), 160.2 (d,
J = 245.0 Hz). HRMS (ESI) calcd for C12H9ClF5NOSNa [M + Na]+
367.9906, found 367.9904.
4.2.12. (4S,Ss)-N-(2-Chlorotetrafluoroethanesulfinyl)-4-(2-
furyl)but-1-yne-4-amine (7l)
Colorless oil. FT-IR (film) 3293, 2923, 1611, 1423, 1257, 1177,
1017, 914, 799, 734, 651 cmꢀ1. 1H NMR (CDCl3, 300 MHz)
d (ppm)
2.08 (d, J = 2.6 Hz, 1H), 2.82–2.84 (m, 2H), 4.79 (dd, J = 14.3, 6.8 Hz,
1H), 5.21 (d, J = 7.8 Hz, 1H), 6.34 (dd, J = 3.3, 1.7 Hz, 1H), 6.41 (d,
J = 3.3 Hz, 1H), 7.40 (dd, J = 0.8, 0.8 Hz, 1H). 19F NMR (CDCl3,
4.2.7. (4S,Ss)-N-(2-Chlorotetrafluoroethanesulfinyl)-4-(p-
bromophenyl)but-1-yne-4-amine (7g)
Colorless oil. FT-IR (film) 3296, 2927, 2357, 2121, 1899, 1593,
1489, 1419, 1262, 1165, 799, 669 cmꢀ1. 1H NMR (CDCl3, 300 MHz)
282 MHz)
d
(ppm) ꢀ66.73 (s, 2F), ꢀ115.58 (d, JFF = 233.8 Hz, 1F),
ꢀ120.15 (d, JFF = 233.8 Hz, 1F). 13C NMR (CDCl3, 100 MHz)
d (ppm)
d
(ppm) 2.11 (t, J = 1.2 Hz, 1H), 2.76–2.80 (m, 2H), 4.77 (dd, J = 11.9,
26.0, 51.4, 72.4, 78.6, 108.4, 110.6, 143.1, 151.6. HRMS (ESI) calcd
for C10H8ClF4NO2SNa [M + Na]+ 339.9793, found 339.9808.
5.9 Hz, 1H), 5.14 (d, J = 6.0 Hz, 1H), 7.26 (d, J = 6.9 Hz, 2H), 7.52 (d,
J = 8.1 Hz, 2H). 19F NMR (CDCl3, 282 MHz)
d
(ppm) ꢀ66.57 (s, 2F),
ꢀ114.91 (d, JFF = 233.8 Hz, 1F), ꢀ120.29 (d, JFF = 233.8 Hz, 1F). 13C
4.2.13. (4S,Ss)-N-(2-Chlorotetrafluoroethanesulfinyl)-4-(2-
thienyl)but-1-yne-4-amine (7m)
Colorless oil. FT-IR (film) 3311, 2926, 1922, 1621, 1427, 1330,
1262, 1170, 907, 793, 667 cmꢀ1. 1H NMR (CDCl3, 400 MHz)
d (ppm)
NMR (CDCl3, 100 MHz) d (ppm) 29.8, 55.3, 73.2, 78.3, 127.7, 128.6,
132.2, 138.3. HRMS (ESI) calcd for C12H9BrClF4NOSNa [M + Na]+
427.9105, found 427.9099.
2.14 (t, J = 2.6 Hz, 1H), 2.82–2.94 (m, 2H), 5.02 (dd, J = 12.8, 6.0 Hz,
1H), 5.18 (d, J = 4.8 Hz, 1H), 7.00 (dd, J = 4.8, 3.6 Hz, 1H), 7.13 (d,
J = 3.6 Hz, 1H), 7.31 (dd, J = 5.2, 1.2 Hz, 1H). 19F NMR (CDCl3,
4.2.8. (4S,Ss)-N-(2-Chlorotetrafluoroethanesulfinyl)-4-(p-
methylphenyl)but-1-yne-4-amine (7h)
Colorless oil. FT-IR (film) 3308, 2925, 2123, 1516, 1428, 1262,
282 MHz)
d
(ppm) ꢀ66.43 (s, 2F), ꢀ114.91 (d, JFF = 232.7 Hz, 1F),
1015, 905, 798, 667 cmꢀ1. 1H NMR (CDCl3, 300 MHz)
d
(ppm) 2.05
ꢀ119.88 (d, JFF = 232.7 Hz, 1F). 13C NMR (CDCl3, 100 MHz)
d (ppm)
(t, J = 1.8 Hz, 1H), 2.33 (s, 3H), 2.73–2.75 (m, 2H), 4.68 (dd, J = 16.9,
6.0 Hz, 1H), 5.22 (d, J = 6.0 Hz, 1H), 7.17 (d, J = 7.8 Hz, 2H), 7.24 (d,
29.0, 53.0, 73.1, 78.6, 126.1, 126.3, 127.2, 142.4. HRMS (ESI) calcd
for C10H8ClF4NOS2Na [M + Na]+ 355.9564, found 355.9557.
J = 7.8 Hz, 2H). 19F NMR (CDCl3, 282 MHz)
d
(ppm) ꢀ66.40 (s, 2F),
ꢀ115.24 (d, JFF = 233.8 Hz, 1F), ꢀ120.08 (d, JFF = 233.8 Hz, 1F). 13C
4.2.14. (4S,Ss)-N-(2-Chlorotetrafluoroethanesulfinyl)-4-
(cyclohexyl)but-1-yne-4-amine (7o)
NMR (CDCl3, 100 MHz)
d (ppm) 21.2, 28.3, 56.5, 72.5, 79.0, 126.8,
129.7, 136.2, 138.6. HRMS (ESI) calcd for C13H12ClF4NOSNa
[M + Na]+ 364.0157, found 364.0153.
Colorless oil. FT-IR (film) 3312, 2926, 2854, 1723, 1452, 1263,
1173, 1014, 907, 795, 736, 648 cmꢀ1. 1H NMR (CDCl3, 300 MHz)
d
(ppm) 1.14–1.28 (m, 3H), 1.56–1.69 (m, 3H), 1.75–1.79 (m, 3H), 1.90
(s, 1H), 2.03–2.07 (m, 1H), 2.45–2.50 (m, 2H), 3.13 (t, J = 2.3 Hz, 1H),
3.24–3.33 (m, 1H), 4.59 (dd, J = 10.2, 9.6 Hz, 1H). 19F NMR (CDCl3,
4.2.9. (4S,Ss)-N-(2-Chlorotetrafluoroethanesulfinyl)-4-(p-
phenylphenyl)but-1-yne-4-amine (7i)
Colorless oil. FT-IR (film) 3299, 2361, 1600, 1488, 1420, 1262,
282 MHz)
d
(ppm) ꢀ66.68 (s, 2F), ꢀ115.21 (d, JFF = 234.9 Hz, 1F),
1016, 905, 797, 736, 698 cmꢀ1; 1H NMR (CDCl3, 300 MHz)
d
(ppm)
ꢀ122.10 (d, JFF = 234.9 Hz, 1F). 13C NMR (CDCl3, 100 MHz)
d (ppm)
2.14 (d, J = 2.4 Hz, 1H), 2.85 (t, J = 3.0 Hz, 2H), 4.83 (dd, J = 12.0,
5.7 Hz, 1H), 5.36 (d, J = 6.9 Hz, 1H), 7.36–7.48 (m, 5H), 7.61 (d,
24.4, 26.1, 28.8, 29.7, 41.5, 60.6, 71.7, 76.3, 78.2. HRMS (ESI) calcd for
C
12H16ClF4NOSNa [M + Na]+ 356.0470, found 356.0467.
J = 7.8 Hz, 2H), 7.63 (d, J = 7.8 Hz, 2H). 19F NMR (CDCl3, 282 MHz)
d
(ppm) ꢀ66.05 (s, 2F), ꢀ114.61 (d, JFF = 233.8 Hz, 1F), ꢀ119.78 (d,
4.2.15. (4S,Ss)-N-(2-Chlorotetrafluoroethanesulfinyl)-4-
(isopropyl)but-1-yne-4-amine (7p)
JFF = 233.8 Hz, 1F). 13C NMR (CDCl3, 100 MHz)
d
(ppm) 28.3, 56.3,
72.7, 78.9, 127.3, 127.6, 127.7, 127.8, 128.9, 138.2, 140.4, 141.6.
HRMS (ESI) calcd for C18H14ClF4NOSNa [M + Na]+ 426.0313, found
426.0308.
Colorless oil. FT-IR (film) 3313, 2967, 1467, 1263, 1177, 1012,
908, 795, 647 cmꢀ1 1H NMR (CDCl3, 300 MHz)
. d (ppm) 1.01 (d,
J = 1.8 Hz, 3H), 1.03 (d, J = 1.8 Hz, 3H), 1.25 (s, 1H), 2.05 (t, J = 2.9 Hz,
1H), 2.49 (dd, J = 5.6, 2.6 Hz, 2H), 3.29–3.37 (m, 1H), 4.58 (d,
4.2.10. (4S,Ss)-N-(2-Chlorotetrafluoroethanesulfinyl)-4-(p-
trifluoromethylphenyl)but-1-yne-4-amine (7j)
J = 9.0 Hz, 1H). 19F NMR (CDCl3, 282 MHz)
d
(ppm) ꢀ66.68 (s, 2F),
ꢀ115.18 (d, JFF = 234.6 Hz, 1F), ꢀ122.03 (d, JFF = 234.6 Hz, 1F). 13C
Colorless oil. FT-IR (film) 3174, 2923, 1621, 1428, 1327, 1263,
NMR (CDCl3, 100 MHz) d (ppm) 18.3, 19.4, 24.5, 31.9, 60.8, 71.7,
1178, 1069, 908, 844, 801, 604 cmꢀ1
.
1H NMR (CDCl3, 300 MHz)
d
79.4. HRMS (ESI) calcd for C9H12ClF4NOSNa [M + Na]+ 316.0157,
found 316.0163.
(ppm) 2.11 (t, J = 2.6 Hz, 1H), 2.71–2.89 (m, 2H), 4.88 (dd, J = 12.5,
5.9 Hz, 1H), 5.45 (d, J = 7.5 Hz, 1H), 7.51 (d, J = 8.1 Hz, 2H), 7.65 (d,
J = 8.1 Hz, 2H). 19F NMR (CDCl3, 282 MHz)
d
(ppm) ꢀ62.40 (s, 3F),
ꢀ66.62 (s, 2F), ꢀ114.31 (d, JFF = 237.7 Hz, 1F), ꢀ120.53 (d,
JFF = 237.7 Hz, 1F). 13C NMR (CDCl3, 100 MHz)
(ppm) 28.5,
4.2.16. (4S,Ss)-N-(2-Chlorotetrafluoroethanesulfinyl)-4-(2-
phenylvinyl)but-1-yne-4-amine (7q)
d
White powder. mp 31–32 8C. FT-IR (KBr) 3274, 2915, 1494,
55.1, 73.3, 78.1, 125.9 (q, J = 3.7 Hz), 127.3, 127.7, 130.9 (q,
J = 32.3 Hz), 143.3. HRMS (ESI) calcd for C13H9ClF7NOSNa [M + Na]+
417.9874, found 417.9860.
1259, 1172, 1015, 970, 907, 747, 692 cmꢀ1 1H NMR (CDCl3,
.
300 MHz)
d (ppm) 2.13 (dd, J = 3.5, 1.7 Hz, 1H), 2.57–2.73 (m, 2H),
4.35 (ddd, J = 12.9, 6.3, 6.3 Hz, 1H), 4.97 (d, J = 7.8 Hz, 1H), 6.25 (dd,
J = 15.9, 6.6 Hz, 1H), 6.68 (d, J = 15.9 Hz, 1H), 7.24–7.30 (m, 3H),
4.2.11. (4S,Ss)-N-(2-Chlorotetrafluoroethanesulfinyl)-4-(p-
methoxyphenyl)but-1-yne-4-amine (7k)
Colorless oil. FT-IR (film) 3293, 2927, 2277, 1612, 1517, 1251,
1176, 1015, 797, 650 cmꢀ1. 1H NMR (CDCl3, 300 MHz)
d (ppm) 2.09
(t, J = 2.6 Hz, 1H), 2.75–2.78 (m, 2H), 3.80 (s, 3H), 4.70 (dd, J = 12.0,
6.0 Hz, 1H), 5.16 (d, J = 5.7 Hz, 1H), 6.90 (d, J = 8.7 Hz, 2H), 7.30 (d,
7.33–7.41 (m, 2H). 19F NMR (CDCl3, 282 MHz)
d
(ppm) ꢀ69.20 (s,
2F), ꢀ118.15 (d, JFF = 233.8 Hz, 1F), ꢀ122.71 (d, JFF = 233.8 Hz, 1F).
13C NMR (CDCl3, 100 MHz)
(ppm) 27.2, 55.2, 72.6, 78.7, 126.9,
127.1, 128.5, 128.8, 133.6, 135.9. HRMS (ESI) calcd for
14H12ClF4NOSNa [M + Na]+ 376.0156, found 376.0167.
d
C
J = 8.7 Hz, 2H). 19F NMR (CDCl3, 282 MHz)
d
(ppm) ꢀ66.70 (s, 2F),
4.2.17. (4S,Ss)-N-(2-Chlorotetrafluoroethanesulfinyl)-4-(2-
phenylvinyl)but-1-yne-4-amine (7q0)
ꢀ115.83 (d, JFF = 233.5 Hz, 1F), ꢀ120.23 (d, JFF = 233.5 Hz, 1F). 13C
NMR (CDCl3, 100 MHz)
d
(ppm) 28.3, 55.4, 56.4, 72.5, 79.1, 114.4,
White powder. mp 40–42 8C. FT-IR (film) 3305, 2924, 1738,
128.2, 131.2, 159.9. HRMS (ESI) calcd for C13H12ClF4NO2SNa
[M + Na]+ 380.0106, found 380.0120.
1365, 1230, 909, 798, 693 cmꢀ1. 1H NMR (CDCl3, 300 MHz)
d
(ppm)
1.03 (d, J = 1.8 Hz, 3H), 1.25 (s, 1H), 2.05 (t, J = 2.9 Hz, 1H), 2.49

L.-J. Liu, J.-T. Liu / Journal of Fluorine Chemistry 168 (2014) 44–49
49
(dd, J = 5.6, 2.6 Hz, 2H), 2.18 (dd, J = 2.6, 2.6 Hz, 1H), 2.57–2.75
(m, 2H), 4.35 (ddd, J = 12.3, 6.1, 6.1 Hz, 1H), 4.93 (d, J = 5.1 Hz, 1H),
6.10 (dd, J = 15.9, 7.7 Hz, 1H), 6.71 (d, J = 16.2 Hz, 1H), 7.29–7.42
CuSO4 (5.0 mL ꢂ 3), water (5.0 mL) and brine in sequence. The
organic phrase was dried over anhydrous Na2SO4, concentrated
and purified by column chromatography (EA/PE: 1/5) to give 9b.
(m, 5H). 19F NMR (CDCl3, 282 MHz)
d
(ppm) ꢀ66.42 to ꢀ66.53 (m,
2F), ꢀ117.30 (d, JFF = 233.5 Hz, 1F), ꢀ118.73 (d, JFF = 233.5 Hz, 1F).
13C NMR (CDCl3, 100 MHz)
(ppm) 27.1, 55.9, 72.9, 78.7, 126.3,
126.9, 128.7, 128.9, 134.8, 135.7. HRMS (ESI) calcd for
14H12ClF4NOSNa [M + Na]+ 376.0156, found 376.0149.
4.4.1. (4S)-N-(p-methylphenylsulfonyl)-4-phenylbut-1-yne-4-amine
(9b)
d
Colorless oil. 1H NMR (CDCl3, 300 MHz)
d (ppm) 1.98 (t,
C
J = 2.4 Hz, 1H), 2.38 (s, 3H), 2.64 (dd, J = 5.9, 2.6 Hz, 2H), 4.50 (dd,
J = 12.6, 6.3 Hz, 1H), 5.24 (d, J = 7.2 Hz, 1H), 7.22–7.17 (m, 7H), 7.62
(d, J = 8.1 Hz, 2H). EI-MS (m/z, %) 260 (64.46), 155 (54.66), 91
4.2.18. (3S,4S,Ss)-N-(2-Chlorotetrafluoroethanesulfinyl)-1-phenyl-
4-(4-chlorophenyl)but-1-yne-4-amine (7s)
(100.00). ½a 2D6
ꢀ60.4 (c 1.0, CHCl3).
ꢁ
White powder. mp 70–71 8C. FT-IR (KBr) 3223, 2896, 1597,
1492, 1264, 916, 794, 755, 690 cmꢀ1 1H NMR (300 MHz, CDCl3)
. d
Acknowledgement
(ppm) 2.87–2.96 (m, 2H), 4.80 (dd, J = 12.9, 6.0 Hz, 1H), 5.26 (d,
J = 14.1 Hz, 1H), 7.25–7.36 (m, 9H). 19F NMR (282 MHz, CDCl3)
(ppm) ꢀ66.77 (s, 2F), ꢀ114.99 (d, JFF = 233.8 Hz, 1F), ꢀ120.61 (d,
JFF = 233.8 Hz, 1F). 13C NMR (100 MHz, CDCl3)
(ppm) 29.5, 55.6,
d
Financial support from the National Natural Science Foundation
of China (No. 21172243) is gratefully acknowledged.
d
83.6, 85.0, 122.7, 128.3, 128.4, 128.5, 129.2, 131.7, 134.6, 138.1.
HRMS (EI) calcd for C18H13Cl2F4NOSNa [M + Na]+ 459.9923, found
459.9942.
Appendix A. Supplementary data
Supplementary material related to this article can be found, in the
online version, at http://dx.doi.org/10.1016/j.jfluchem.2014.08.008.
4.2.19. (S,Ss)-N-(2-Chlorotetrafluoroethanesulfinyl)-1-(4-
chlorophenyl)-2-methylbuta-2,3-dien-1-amine (7t)
Colorless oil. FT-IR (film) 3224, 2921, 1959, 1597, 1261, 1165,
1015, 909 cmꢀ1. 1H NMR (300 MHz, CDCl3)
d
(ppm) 1.57–1.62 (m,
References
3H), 4.95–5.02 (m, 4H), 7.25–7.40 (m, 4H). 19F NMR (282 MHz,
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d
(ppm) ꢀ66.70 (s, 2F), ꢀ115.96 (d, JFF = 236.9 Hz, 1F),
ꢀ119.60 (d, JFF = 236.9 Hz, 1F). 13C NMR (100 MHz, CDCl3)
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907, 792, 668 cmꢀ1. 1H NMR (300 MHz, CDCl3)
d
(ppm) 1.03 (s, 3H),
1.42 (s, 3H), 2.37 (s, 1H), 4.19 (d, J = 9.0 Hz, 1H), 5.35 (d, J = 8.7 Hz,
1H), 7.26–7.36 (m, 4H). 19F NMR (282 MHz, CDCl3)
(ppm) ꢀ66.85
(s, 2F), ꢀ113.13 (d, JFF = 247.5 Hz, 1F), ꢀ121.71 (d, JFF = 247.5,
4.3 Hz, 1F). 13C NMR (100 MHz, CDCl3)
(ppm) 26.8, 28.7, 37.4,
64.1, 73.2, 86.6, 128.6, 129.6, 134.6, 136.9. HRMS (ESI) calcd for
14H13Cl2F4NOSNa [M + Na]+ 411.9923, found 411.9937.
d
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4.4. Procedure for the synthesis of 9b
A mixture of 7b (0.15 mmol), 4 M HCl (0.5 mL, in dioxane) was
stirred at 45 8C for 1 h (monitored by TLC). After cooled to room
temperature, solvent was removed under reduced pressure, 8b
was obtained as a white solid and used in next step without further
purification.
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