2-Chlorotetrafluoroethanesulfinamide induced asymmetric vinylogous Mannich reaction

Article abstract of DOI:10.1016/j.tet.2013.12.071

The generality of (S)-2-chlorotetrafluoroethanesulfinamide (CTFSA) induced asymmetric vinylogous Mannich (AVM) addition reaction has been investigated. The reaction of aldimines derived from (S)-CTFSA with 2-(tert- butyldimethylsilyloxy) furan (TBSOF) too

Full text of DOI:10.1016/j.tet.2013.12.071

Accepted Manuscript
2-Chlorotetrafluoroethanesulfinamide induced asymmetric vinylogous Mannich
reaction
Li-Juan Liu, Jin-Tao Liu
PII:
S0040-4020(13)01939-X
DOI:
10.1016/j.tet.2013.12.071
TET 25155
Reference:
To appear in: Tetrahedron
Received Date: 13 September 2013
Revised Date: 13 December 2013
Accepted Date: 24 December 2013
Please cite this article as: Liu L-J, Liu J-T, 2-Chlorotetrafluoroethanesulfinamide induced asymmetric
vinylogous Mannich reaction, Tetrahedron (2014), doi: 10.1016/j.tet.2013.12.071.
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(S)-2-Chlorotetrafluoroethanesulfinamide
induced
2-(tert-butyldimethylsilyloxy)
furan-based asymmetric vinylogous Mannich reaction was studied. The reaction gave the
corresponding adduct in syn-configuration in good yield with high stereoselectivity in DMSO.
However, anti-isomer was obtained as the major product in the presence of
t
(
TBAF)( BuOH) .
2
.6
1

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2
-Chlorotetrafluoroethanesulfinamide induced asymmetric
vinylogous Mannich reaction
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Li-Juan Liu and Jin-Tao Liu*
Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy
of Sciences, 345 Lingling Road, Shanghai 200032, P. R. China
jtliu@sioc.ac.cn
Abstract
The generality of (S)-2-chlorotetrafluoroethanesulfinamide (CTFSA) induced asymmetric
vinylogous Mannich (AVM) addition reaction has been investigated. The reaction of
aldimines derived from (S)-CTFSA with 2-(tert-butyldimethylsilyloxy) furan (TBSOF) took
place regioselectively at the γ-site at room temperature in DMSO under air atmosphere to
give the desired addition products in syn-configuration with high diastereoselectivities (up
to 98:2 dr). However, anti-configuration product as major isomer was obtained in the
o
presence of tetra-butyl ammonium fluoride (TBAF) at -78 C. Facile removal of the
auxiliary group without epimerization demonstrated their synthetic potential for piperidone
derivatives.
Keywords: 2-chlorotetrafluoroethanesulfinamide, vinylogous Mannich reaction, chiral
auxiliary, asymmetric synthesis
2

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1
. Introduction
1
Thanks to the pioneering work by Casiraghi et al., 2-trialkylsilyloxyfuran-based
2
asymmetric vinylogous Mannich-type reaction (AVMR) of imines is being increasingly
employed for the preparation of γ-butenolide derivatives bearing an amine functionality, a
valuable class of intermediates for the synthesis of alkaloids and other nitrogen-containing
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compounds. In 1999, Martin and Lopez have succeeded in developing the first catalytic
and asymmetric vinylogous Mannich reaction involving silyloxyfurans and aryl aldimines.
5
Since then, catalytic methods have been well developed.
Nowadays, the chiral auxiliary strategy is still an important technology in asymmetric
synthesis from the practical point of view, because the separation of diastereomeric
products prior to the cleavage of the chiral auxiliary provides enantiomerically pure
6
products. However, to the best of our knowledge, there are only two reported examples
about chiral auxiliary induced AVM reaction of 2-trialkylsilyloxy furans with aldimines.
One case corresponds to the reaction of aldimines with 2-(trimethylsilyloxy)furan (TMSOF)
using O-pivaloylated D-galactosylamine as the chiral auxiliary. High yields and good
o
6
enantioselectivities were achieved using ZnCl ·Et O as the promoter at -78 C. Recently,
2
2
7
t
8
Davis's N-p-toluenesulfinimines and Ellman's N-tert-butanesulfinimines ( BS-imines)
have gained a great success as versatile chiral amine templates. In 2011, TBSOF-based
t
vinylogous Mannich reaction with chiral tert-butanesulfinimines ( BS-imines) was reported
and applied to synthesize a key intermediate in the asymmetric synthesis of the potent
γ-secretase inhibitor L-685, 458 and to constitute a formal asymmetric synthesis of
9
(‒ )-deoxoprosophyline and other alkaloids. Although excellent yields and high
stereoselectivities were achieved in these two transformations, low temperature and Lewis
acids were required.
In our recent studies, 2-chlorotetrafluoroethanesulfinamide (CTFSA) has been proved as
1
0
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a promising auxiliary in Strecker reaction, three component aza Diels-Alder reaction and
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aminoallylation of aldehydes. Superiorities of imines endowed by fluorinated alkyl groups
3

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lie in three aspects: (1) the derived imines have high reactivity toward nucleophiles and the
reactions usually take place under mild conditions to afford good yields and high
diastereoselectivities; (2) the polyfluoroalkanesulfinyl group in the product is much easier
to remove; (3) the reaction progress and diastereoselectivity can be conveniently monitored
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by F NMR spectroscopy without work-up of the reaction mixture. As an extension of the
application study of CTFSA, we next studied the trialkylsilyloxyfuran-based AVM reaction
using (S)-CTFSA as the chiral auxiliary.
2
. Results and Discussion
Our preliminary study was conducted by the addition of TBSOF (2a) to
N-(p-chlorobenzylidene)-2-chlorotetrafluoroethanesulfinamide (1a) under the conditions
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t
9
developed for BS-imines. 1a was treated with 2.0 equiv of TBSOF (2a) and 1.0 equiv of
o
trimethylsilyl trifluoromethanesulfonate (TMSOTf) in dichloromethane (DCM) at -78 C
1
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for 2 hours (Table 1, entry 1). Unfortunately, only the starting material was observed by F
NMR spectrum analysis of the reaction mixture. No reaction occurred at elevated
o
i
temperature (25 C), either. Using Ti(O Pr) as Lewis acid also failed to afford the expected
4
products in DCM or ethereal solvent such as THF and 1,4-dioxane, even if the temperature
o
i
was raised to 60 C (entries 2-4). When InCl was used instead of Ti(O Pr) , the result was
3 4
still frustrating (entry 5). Trace of adduct 3 was observed when Sc(OTf) was added after 12
3
hours (entry 6).
Further examination of solvent revealed that both N,N-dimethylformamide (DMF) and
N,N'-dimethylpropyleneurea (DMPU) were successful to provide the desired adducts 3a
and 3a' as a pair of diastereomers in the absence of Lewis acid, although in low yields with
poor diastereoselectities (Table 1, entries 7 and 8). The yields of adducts could not be
improved by prolonging the reaction time or elevating the reaction temperature. Gratefully,
the reaction in DMSO proceeded well to give adducts 3a and 3a' in a total yield of 88%
with a dr of 92:8 at room temperature (entry 9). Using HMPA as solvent, isomers were
4

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obtained in 74% yield with 77:23 dr (entry 10). Decreasing the temperature to 5 C had a
slight improvement on the reaction, leading to a yield of 84% with a dr of 81:19 (entry 11).
Using 2-(trimethylsilyloxy)furan (TMSOF) instead of 2a, the reaction time was
shortened to 12 hours, but the diastereoselectivity was lowered to 79:21 (Table 1, entry 12).
Finally, the optimal reaction conditions were defined as treating a DMSO solution of 1a
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(
1.0 equiv) with 2a (2.0 equiv) at room temperature.
Table 1. Optimization of the reaction conditions
a
o
b
c
c
Entry
Solvent
DCM
DCM
THF
Additive
T ( C)
t (h)
2
Conv. (%)
Yield (%)
dr (3a/3a')
1
2
3
4
5
6
7
8
9
1
1
1
1
TMSOTf
-78
0
0
---
i
Ti(O Pr)
rt ~ 60
rt ~ 60
rt ~ 60
rt ~ 60
rt ~ 60
rt ~ 60
rt
4
0
0
---
4
i
Ti(O Pr)
4
0
0
---
4
i
1,4-dioxane Ti(O Pr)4
4
0
0
---
DCM
InCl3
Sc(OTf)3
none
4
0
0
---
DCM
12
15
15
37
24
21
12
37
9
trace
44
14
88
74
84
98
0
---
DMF
49
14
88
94
100
100
0
57:43
---
DMPU
DMSO
HMPA
HMPA
DMSO
DMSO
none
none
rt
92:8
77:23
81:19
79:21
---
0
1
2
3
none
rt
none
5
d
e
none
rt
none
rt
5

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a
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Reaction Conditions: 1a (0.5 mmol), 2a (1.0 mmol), additive (0.5 mmol) and solvent (1.0 mL);
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d
Conversion of the imine; Determined by F NMR of the reaction mixture; 2-(Trimethylsilyloxy)furan
e t
(
TMSOF) was used instead of 2a, BS-imine prepared from TBSA and 4-chlorobenzyl aldehyde was
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used as the substrate.
The X-ray crystal structure of the major product 3a prepared with racemic 1a in DMSO
revealed the syn-configuration of the new generated chiral centers (Figure 1). Thus, the
absolute configuration of the major product 3a in Table 1 could be assigned as Ss, 4R, 5R
when (S)-1a was used in the reaction.
Figure 1. X-ray structure of the product 3a (Hydrogen atoms were omitted for clarity)
t
It is worth mentioning that no reaction occurred for the corresponding BS-imine
prepared from tert-butanesulfinamide (TBSA) and 4-chlorobenzyl aldehyde under the
optimal reaction conditions (Table 1, entry 13). It was reported that stoichiometric TMSOTf
t
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was necessary for the reaction of BS-imine with 2a. The results further evidence that
2
-chlorotetrafluoroethyl group could enhance the electrophilicity of the corresponding
imines toward nucleophiles. On the other hand, the α-addition product was not observed by
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inspection of the F NMR spectrum of the reaction mixture.
With the optimized conditions in hands, we examined the scope of aldimines and the
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results are summarized in Table 2. The addition reaction tolerated a broad range of
functional groups and high stereoselectivities (up to 98:2 dr) were achieved with aromatic
imines. The electronic nature of the imines 1 had a significant influence on the reaction. For
instance, full conversion of electron-deficient imine 1t derived from 4-cyanobenzaldehyde
was achieved within 2 hours (entry 20). However, it took two weeks for the reaction of
electron-rich imine 1p bearing methoxyl group to go completion (entry 16). The hindered
imine 1v prepared from 1-naphthaldehyde worked well and afforded products in a yield of
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3% with 94:6 dr (entry 22). Heteroaromatic imine 1w was a competent acceptor and
showed only a minor decrease in selectivity (entry 23). The reaction of 1x derived from
iso-valeraldehyde with 2a also afforded the corresponding products in 75% yield with 84:16
dr (entry 24), but the reaction of aldimine 1y derived from pivaldehyde didn’t occurr due to
the steric hindrance (entry 25).
Table 2. (S)-CTFSA induced AVM reactions of aldimines 1 with 2a.
a
b
c
d
Entry
1
R
σ
t [h]
144
35
18
67
20
6
Yield of 3 [%]
dr
1
2
1b
1c
1d
1a
1e
1f
C H
0
88
87
85
90
84
88
81
82
79
90
89
93:7
92:8
91:9
93:7
91:9
93:7
92:8
93:7
94:6
92:8
94:6
6
5
o-ClC H4
6
3
m-ClC H4
0.37
0.24
6
4
p-ClC H4
6
5
2,4-ClC H3
6
6
o-FC H4
6
7
1g
1h
1i
m-FC
H
6
0.34
0.15
5
4
8
p-FC H4
29
19
17
23
6
9
o-BrC H4
6
10
1j
m-BrC H4
0.37
0.26
6
11
1k
p-BrC H4
6
7

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1l
o-MeC H4
242
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79
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-0.14
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o-MeOC H4
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p-MeOC H4
-0.12
336
4
6
1
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o-CF C H
4
3
6
1
m-CF C H
0.46
0.53
0.70
3
3
6
4
19
1s
p-CF C H
4
3
6
4
20
1t
p-NCC H4
2
6
21
1u
1v
1w
1x
1y
o-allylC
H
6
216
63
216
38
12
4
2
2
2
3
naphthyl
thienyl
i
24
Bu
t
2
5
Bu
a
o
b
c
Reaction Conditions: 1 (0.5 mmol), 2a (1.0 mmol), DMSO (1.0 mL), 25 C; Hammett constant;
d
19
Isolated yields; The dr value was determined by F NMR spectroscopy.
9
Based on the above results and the data reported in literature, the dr value of aromatic
imines induced by (S)-CTFSA is superior to that induced by (S)-TBSA. Taking 1a and 1e as
examples, the dr value induced by (S)-CTFSA was 93:7 and 91:9, respectively (entries 4
and 5), while the dr value was 81:19 for both substrates in the case of (S)-TBSA.
In the above AVM reactions, high γ-site selectivity was observed exclusively owing to
14
the higher nucleophilicity of C(4). The reactivity trend of imines in these vinylogous
reactions can be revealed by the reaction time. As shown in Table 2, the reaction time has a
relation with the electronic character of imines. The shorter reaction time was required for
imines with electron-deficient groups. The imine 1t bearing a cyano substituent provided
the product in the shortest time (2 h, entry 20). Imines with a trifluoromethyl substituent
afforded the corresponding products in 4 hours (entries 17-19). However, it took more than
one week for imines 1l-1n bearing a methyl group (entries 12-14) to get full conversion.
Especially, in the case of imine 1p with a p-methoxy substituent, the reaction time was
prolonged to two weeks (entry 16). The only exception of this general trend was the imine
1o bearing an o-methoxy group on aromatic subunit, affording the products in 8 hours
(entry 15). This could be illustrated by the combination of conjugate (+C) and inductive
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effect (-I) of methoxy group. It is known that the -I effect of o-methoxy predominates over
+C effect, thus the electrophilicity of 1o was enhanced toward nucleophilic reagent. It was
also found that the reaction of imines with meta, ortho and para halogen substitutes
required different time to get full conversion. For example, it took 18 hours for imine 1d
(with m-chloro-substitution) and 35 hours for imine 1c (with o-chloro-substitution) to
achieve full conversion, while the reaction of p-chloro-substituted imine 1a required 67
hours (entries 2-4).
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1
6
Further investigation of literatures showed that the reaction time of aldimines bearing
meta or para substituted aryl group was related to the Hammete substituent constant (σ)
value. The higher the σ value, the shorter time is required.
In order to shorten the reaction time, we further tried the reaction in the presence of
fluorine anion, a frequently-used promoter for silyl ethers. Anhydrous KF and CsF had no
effect on the reaction. However, the corresponding adducts were obtained in a total yield of
t
17
6
8% with a dr of 85:15 when 0.1 equiv of (TBAF)( BuOH)2.6 was added to the reaction of
o
1
b and 2a in THF at -78 C (Table 3, entry 1). Simultaneously, the hydrolysis of 1b
occurred and gave the by-product in 10% yield. Increasing the amount of
t
(
TBAF)( BuOH) to 0.6 equiv, the addition reaction was accelerated to give the adducts in
2.6
83% yield with 89:11 dr, indicating that the hydrolysis reaction was successfully restrained
(entry 2). However, no adduct was observed in the presence of 1.0 equiv of
t
(TBAF)( BuOH)
and only hydrolysis product was obtained (entry 3). Similar
2
.6
stereoselectivity and a little lower yield (76%) were obtained when DMSO was used as a
co-solvent (entry 4). The addition of ethyl alcohol made the yield much lower but increased
the dr to 90:10 (entry 5). Using ethyl alcohol as solvent, adduct 3b" was obtained in 66%
yield, although the stereoselectivity was excellent (entry 6). In the case of imine 1a, the
reaction afforded the adduct 3a" as the only product in 56% yield in ethyl alcohol under
similar conditions (entry 7).
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Table 3. Fluoride anion assisted AVM reaction of 1 with TBSOF (2a)
1
1
1
1
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a
a
a
Entry
1
Solvent
Equiv of TBAF
Yield [3", %]
3b", 68
3b", 83
3b", 0
dr
Hydrolysis [%]
1
2
3
4
5
6
1b
1b
1b
1b
1b
1b
1a
THF
0.1
0.6
1.0
0.6
0.6
0.6
0.6
85:15
89:11
---
10
0
THF
THF
100
---
---
19
0
DMSO/THF(1:4)
EtOH/THF(1:4)
EtOH
3b", 76
3b", 45
3b", 66
3a", 56
88:12
90:10
> 95:5
> 99:1
7
EtOH
a
19
Determined by F NMR spectroscopy analysis of the reaction mixture.
It was interesting to find that the anti-adduct 3b" was formed by X-ray structure
analysis (Figure 2). Thus the absolute configuration of the major product in Table 3 could
be assigned as Ss, 4S, 5R, which was the same as that induced by (S)-tert-butanesulfinyl
9
group.
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Figure 2. X-ray structure of the product 3b'' (Hydrogen atoms were omitted for clarity)
A synthetically relevant advantage of using chiral 2-chlorotetrafluoroethanesulfinyl
auxiliary is the facile deprotection of the product by treating with saturated HCl·Et O
2
solution at room temperature or refluxing in 2 M HCl (in MeOH). Adduct 3a was converted
to (4R, 5R)-amine 4a by releasing the sulfinyl group and the subsequent neutralization
(
Scheme 1).
Scheme 1. Deprotection of 3a.
As an example of synthetic application of this reaction, optically pure piperidone
derivative 6a was prepared from 3a. Hydrogenation of 3a afforded the compound 5a
maintaining the sulfinyl group. Although the reaction required three days to achieve full
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conversion due to the strong electron-withdrawing polyfluoroalkyl group, an excellent yield
was obtained. Continuing to treat 5a with HCl solution (4 M in MeOH) and K
sequence, the optically pure lactam 6a was obtained in 86% yield (Scheme 2).
CO in
3
2
1
1
1
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Scheme 2. Synthesis of 6a from 3a.
Based on the experimental results described above, two possible transition states, which
correspond to Newman projections relatively to the incipient carbon-carbon bond, were
proposed in Figure 3 to account for the high diastereoselectivity of the (S)-CTFSA induced
8
a,17
AVM reaction. As reported in literaures,
S=O bond and C=N bond are in cis conformer
rather than trans-one. When (S)-CTFSA is introduced, the re face of the imines is sterically
shielded by 2-chlorotetrafluoroethyl group, therefore the nucleophile TBSOF approaching
from the si face of imines is the favored conformer. When the reaction is carried out in
DMSO without any additives, the nucleophilic reagent may associate with the aldimine
through silicon atom. As a result, the coordination of silicon with oxygen of S=O bond in
the imine reinforced electrophilic reactivity of the imine toward nucleophilic reagents.
Besides, DMSO may also participate in the favored transition state by coordinating with
silicon atom to enhance the reactivity of nucleophilic reagents and the stereoselectivity. In
the activated complex, to minimize steric interactions, the oxygen of furan is in
anti-configuration with the bulky R substituent. Thus, the imine would react with
silyloxyfuran by an exo-type addition (A) to give the syn adduct as the major diastereomer.
However, the coordination of silicon and oxygen atom was released by the addition of
t
(TBAF)( BuOH)2.6. Thus, the transition state B was favored for the addition of silyloxyfuran
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to imines in the presence of fluorine anion and anti-selective adduct was obtained as the
major isomer.
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Figure 3. Proposed transition states
3
. Conclusion
In summary, the (S)-CTFSA induced asymmetric vinylogous Mannich reactions of
aldimines with 2-(tert-butyldimethylsilyloxy) furan have been studied. These reactions were
characterized by high level of γ-site selectivity. High yields and syn-selective adducts were
obtained as major products in DMSO without any additives at room temperature. However,
t
the addition of (TBAF)( BuOH) afforded anti-selective product as the major isomer.
2.6
Along with the excellent selectivity achieved in the reaction with a variety of imines,
transformation of adducts to optically pure substituted 5-hydroxypiperidin-2-ones showed
the synthetic potential of these AVM reactions.
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4
. Experimental section
4.1. General Information
Anhydrous solvents were obtained by distillation over sodium (THF) or calcium hydride
1
1
1
1
1
1
1
1
1
1
2
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6
6
6
t
(1,4-dioxane, DCM, DMSO and DMF). (TBAF)( BuOH)2.6 was operated in glove box.
Flash column chromatography was performed using 300−400 mesh silica gel according to
standard techniques. Nuclear magnetic resonance spectra were recorded either on 300 or
1
4
00 MHz spectrometers. Chemical shifts for H NMR spectra are reported in ppm from
tetramethylsilane with the solvent resonance as the internal standard (CDCl , δ = 7.26 ppm;
3
19
d -DMSO, δ = 2.50 ppm; d -acetone, δ = 2.05 ppm). F NMR spectra were recorded with
6
6
CFCl as the external standard. Data were reported as follows: chemical shift, multiplicity (s
3
=
singlet, d = doublet, t = triplet, m = multiplet), coupling constant in Hz and integration.
13
Chemical shifts for C NMR spectra were reported in ppm using the central peak of CDCl
3
(77.16 ppm), d -DMSO (39.52 ppm) and d -acetone 29.84 ppm). IR spectra were obtained
6 6
with a Nicolet AV-360 spectrophotometer. HRMS data were obtained on a high-resolution
mass spectrometer in the ESI or EI mode.
4
.2. General procedure for the synthesis of imines 1a-y
To a 10 mL round-bottomed flask equipped with a magnetic stir bar were added
(S)-CTFSA (3.0 mmol) and Titanium (IV) isopropoxide (4.5 mmol) in CH Cl (3.0 mL),
2 2
followed by the addition of aldehyde (3.0 mmol). The mixture was stirred at room
temperature and monitored by TLC. After completion of the reaction, brine (5.0 mL) was
added, and the mixture was filtered through celite. The filter cake was washed with CH Cl .
2
2
The aqueous phase was extracted with CH Cl (5.0 mL×3), and the combined organic phase
2
2
was dried over Na SO , concentrated, purified by flash column chromatography (EtOAc/
2
4
petroleum ether: 1/20) to give the corresponding product.
4
.2.1. (S)-N-(p-chlorobenzylidene)-2-chlorotetrafluoroethanesulfinamide (1a). Yield:
-1
1
8
8%; White solid; mp 82−83 °C; FT-IR (KBr) 1593, 1144, 788 cm ; H NMR (300 MHz,
19
CDCl ): δ 8.78 (s, 1H), 7.86 (d, J = 8.7 Hz, 2H), 7.51 (d, J = 8.7 Hz, 2H); F NMR (282
3
1
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MHz, CDCl ): δ -66.75 (s, 2F), -116.33 (d, J = 232.4 Hz, 1F), -117.70 (d, J = 232.4 Hz,
3
FF
FF
1
3
1F); C NMR (100 MHz, CDCl
): δ 166.0, 141.1, 131.9, 131.8 130.1, 130.0; EI-MS (m/z,
Cl NOS: C, 33.56; H, 1.56; N, 4.35.
3
+
%) 321 (M , 0.50), 186 (100); Anal. Calcd for C
H
F
2 4
9
5
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
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6
6
6
6
6
2
6
Found: C, 33.60; H, 1.55; N, 4.34; [α] = -119.92 (c 1.05, CHCl3).
D
4.2.2. (S)-N-(benzylidene)-2-chlorotetrafluoroethanesulfinamide (1b). Yield: 98%;
-1 1
White solid; mp 68−69 °C; FT-IR (KBr) 1600, 1597, 804, 763, 689 cm ; H NMR (300
MHz, CDCl ): δ 8.82 (s, 1H), 7.92 (dd, J = 5.0, 3.2 Hz, 2H), 7.66−7.60 (m, 1H), 7.56−7.51
3
19
(
m, 2H); F NMR (282 MHz, CDCl ): δ -66.25 (s, 2F), -116.04 (d, J = 227.0 Hz, 1F),
3 FF
1
3
-
117.59 (d, J = 227.0 Hz, 1F); C NMR (100 MHz, CDCl ): δ 167.2, 134.3, 133.3, 130.6,
FF 3
1
2
4
4
9
29.3, 122.9 (tt, J = 299.4, 33.2 Hz), 117.3 (ddt, J = 311.1, 301.6, 36.1 Hz); EI-MS (m/z, %)
+
87 (M , 0.19), 152 (100), 135, 104; Anal. Calcd for C H ClF NOS: C, 37.58; H, 2.10; N,
9
6
4
26
.95. Found: C, 37.80; H, 2.11; N, 4.84; [α] = -89.52 (c 1.05, CHCl3).
D
.2.3. (S)-N-(o-chlorobenzylidene)-2-chlorotetrafluoroethanesulfinamide (1c). Yield:
-1 1
3%; Colorless oil; FT-IR (film) 1590, 1177, 757 cm ; H NMR (300 MHz, CDCl ): δ 9.27
3
19
(
s, 1H), 8.11 (d, J = 7.8 Hz, 1H), 7.53−7.45 (m, 2H), 7.40−7.35 (m, 1H); F NMR (282
MHz, CDCl ): δ -66.05 (s, 2F), -115.01 (d, J = 229.5 Hz, 1F), -117.24 (d, J = 229.5 Hz,
3
FF
FF
1
3
1
F); C NMR (100 MHz, CDCl ): δ 163.9, 137.7, 135.0, 130.5, 130.4, 129.9, 127.5;
3
+
26
HRMS (ESI) Calcd for C
H ClNOS [M-C F Cl] 185.9780, found 185.9778; [α] =
5 2 4 D
7
+8.74 (c 1.00, CHCl3).
4.2.4. (S)-N-(m-chlorobenzylidene)-2-chlorotetrafluoroethanesulfinamide (1d). Yield:
-1 1
88%; White solid; mp 41−42 °C; FT-IR (KBr) 1600, 1361, 1166, 895, 794 cm ; H NMR
300 MHz, CDCl ): δ 8.77 (s, 1H), 7.92 (s, 1H), 7.78 (d, J = 7.8 Hz, 1H), 7.59 (d, J = 8.1
(
3
19
Hz, 1H), 7.48 (dd, J = 7.8, 8.1 Hz, 1H); F NMR (282 MHz, CDCl ): δ -65.97 (s, 2F),
3
1
3
-
115.47 (d, JFF = 228.7 Hz, 1F), -116.64 (d, JFF = 228.7 Hz, 1F); C NMR (100 MHz,
CDCl ): δ 165.9, 135.6, 134.7, 134.1, 130.6, 129.8, 128.9; HRMS (ESI) Calcd for
3
26
C H Cl F NOS 320.9405, found 320.9401; [α] = -96.81 (c 1.00, CHCl3).
9
5
2
4
D
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.2.5. (S)-N-(2,4-dichlorobenzylidene)-2-chlorotetrafluoroethanesulfinamide (1e). Yield:
-1 1
83%; White solid; mp 67−68 °C; FT-IR (KBr) 1600, 1473, 1262, 866, 797 cm ; H NMR
(300 MHz, CDCl ): δ 9.22 (s, 1H), 8.08 (d, J = 8.4 Hz, 1H), 7.53 (s, 1H), 7.40 (d, J = 8.4
Hz, 1H); F NMR (282 MHz, CDCl ): δ -66.00 (s, 2F), -114.78 (d, J = 229.1 Hz, 1F),
3
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1
1
1
1
1
1
1
1
2
2
2
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2
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2
2
2
3
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3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
6
6
6
6
6
19
3
FF
1
3
-116.84 (dt, J = 229.1, 4.1 Hz, 1F); C NMR (100 MHz, CDCl ): δ 163.0, 141.1, 138.4,
FF
3
1
3
4
9
30.8, 130.5, 129.1, 128.3; HRMS (ESI) Calcd for C H Cl F NOS 354.9015, found
9 4 3 4
2
6
54.9016; [α] = -32.22 (c 1.40, CHCl3).
D
.2.6. (S)-N-(o-fluorobenzylidene)-2-chlorotetrafluoroethanesulfinamide (1f). Yield
-1 1
0%; Colorless oil; FT-IR (film) 1614, 1141, 1031, 762 cm ; H NMR (300 MHz, CDCl ):
3
δ 9.28 (s, 1H), 8.20 (dd, J = 7.5 Hz, 7.5 Hz, 1H), 7.76 (dd, J = 13.8, 7.2 Hz, 1H), 7.46−7.31
19
(m, 2H); F NMR (282 MHz, CDCl ): δ -65.80 (s, 2F), -115.23 (d, J = 229.5 Hz, 1F),
3
FF
13
-116.27 to -116.35 (m, 1F), -116.89 (d, J = 229.5 Hz, 1F); C NMR (100 MHz, CDCl ): δ
FF 3
1
1
3
4
8
64.6, 162.1, 160.9 (d, J = 5.8 Hz), 136.4 (d, J = 9.4 Hz), 129.3, 125.1 (d, J = 3.6 Hz),
21.3 (d, J = 8.8 Hz), 116.6 (d, J = 20.4 Hz); HRMS (ESI) Calcd for C H ClF NOS
9
5
5
2
6
04.9701, found 304.9703; [α]
= -64.36 (c 1.00, CHCl3).
D
.2.7. (S)-N-(m-fluorobenzylidene)-2-chlorotetrafluoroethanesulfinamide (1g). Yield
-1 1
7%; White solid; mp 44−45 °C; FT-IR (KBr) 1603, 1267, 803 cm ; H NMR (300 MHz,
): δ 9.10 (s, 1H), 7.99−7.93 (m, 2H), 7.82 (dd, J = 14.1, 6.9 Hz, 1H), 7.62 (dd, J = 7.4,
CDCl
3
19
7.4 Hz, 1H); F NMR (282 MHz, CDCl ): δ -66.06 (s, 2F), -110.59 to -110.67 (m, 1F),
3
13
-115.16 (d, JFF = 229.5 Hz, 1F), -117.28 (d, JFF = 229.5 Hz, 1F); C NMR (100 MHz,
CDCl ): δ 166.1, 163.1, 135.1 (d, J = 8.0 Hz), 131.1 (d, J = 8.0 Hz), 126.9 (d, J = 2.9 Hz),
3
1
3
4
21.4 (d, J = 21.9 Hz), 116.1 (d, J = 22.6 Hz); HRMS (ESI) Calcd for C H ClF NOS
9 5 5
2
6
04.9701, found 304.9705; [α] = -115.05 (c 1.00, CHCl3).
D
.2.8 (S)-N-(p-fluorobenzylidene)-2-chlorotetrafluoroethanesulfinamide (1h). Yield
-1
7
3%; White solid; mp 72−73 °C; FT-IR (KBr) 1600, 1156, 1139, 1107, 1012, 802, 790 cm ;
1
19
H NMR (300 MHz, CDCl ): δ 8.77 (s, 1H), 7.96−7.92 (m, 2H), 7.26−7.19 (m, 2H); F
3
NMR (282 MHz, CDCl ): δ -66.74 (s, 2F), -102.72 (s, 1F), -116.48 (d, J = 228.1 Hz, 1F),
3
FF
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117.97 (d, J = 228.1 Hz, 1F); C NMR (100 MHz, CDCl ): δ 166.3 (d, J = 256.0 Hz),
F
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3
165.5, 132.8 (d, J = 9.9 Hz), 129.5 (d, J = 2.8 Hz), 116.7 (d, J = 20.8 Hz); HRMS (ESI)
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6
Calcd for C
H ClF NOS 304.9701, found 304.9701; [α] = -82.08 (c 1.50, CHCl ).
5 5 D 3
9
1
1
1
1
1
1
1
1
1
1
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6
4.2.9. (S)-N-(o-bromobenzylidene)-2-chlorotetrafluoroethanesulfinamide (1i). Yield
-1 1
91%; Colorless oil; FT-IR (film) 1698, 1265, 1180, 756 cm ; H NMR (300 MHz, CDCl ):
3
δ 9.22 (s, 1H), 8.11 (dd, J = 5.9, 3.8 Hz, 1H), 7.67 (dd, J = 5.9, 3.5 Hz, 1H), 7.45−7.42 (m,
19
2
H); F NMR (282 MHz, CDCl ): δ -65.87 (s, 2F), -115.12 (d, J = 229.0 Hz, 1F), -116.68
3 FF
1
3
(
d, J = 229.0 Hz, 1F); C NMR (100 MHz, CDCl ): δ 166.4, 135.1, 133.9, 131.8, 130.3,
F
F
3
+
1
28.1, 127.6; HRMS (ESI) Calcd for C H BrNOS [M-C F Cl] 229.9275, found 229.9272;
7 5 2 4
26
[
α] = +50.21 (c 1.00, CHCl3).
D
4
8
.2.10. (S)-N-(m-bromobenzylidene)-2-chlorotetrafluoroethanesulfinamide (1j). Yield
-1
1
5%; White solid; mp 33−34 °C; FT-IR (KBr) 1601, 1179, 1012, 796, 679 cm ; H NMR
(
300 MHz, CDCl ): δ 8.75 (s, 1H), 8.06 (s, 1H), 7.82 (d, J = 7.5 Hz, 1H), 7.73 (d, J = 8.1
3
19
Hz, 1H), 7.41 (dd, J = 7.7, 7.7 Hz, 1H); F NMR (282 MHz, CDCl ): δ -65.98 (s, 2F),
3
13
-
115.52 (d, JFF = 228.4 Hz, 1F), -116.59 (d, JFF = 228.4 Hz, 1F); C NMR (100 MHz,
CDCl ): δ 165.8, 137.1, 134.9, 132.8, 130.9, 129.3, 123.6; HRMS (ESI) Calcd for
3
+
26
C
H BrNOS [M-C
5
F Cl] 229.9275, found 229.9278; [α] = -85.50 (c 0.65, CHCl ).
2 4 D 3
7
4.2.11. (S)-N-(p-bromobenzylidene)-2-chlorotetrafluoroethanesulfinamide (1k). Yield
-1 1
89%; White solid; mp 57-59 °C; FT-IR (KBr) 1587, 1141, 1012, 790 cm ; H NMR (300
1
9
MHz, CDCl ): δ 8.77 (s, 1H), 7.78 (d, J = 8.4 Hz, 2H), 7.68 (d, J = 8.4 Hz, 2H); F NMR
3
(282 MHz, CDCl ): δ -65.94 (s, 2F), -115.42 (dt, J = 228.4, 3.1 Hz, 1F), -116.86 (dt, J =
3
FF
FF
1
3
2
28.4, 3.1 Hz, 1F); C NMR (100 MHz, CDCl ): δ 165.8, 132.7, 131.8, 131.6, 129.5;
3
2
6
HRMS (ESI) Calcd for C H BrClF NOS 364.8900, found 364.8904; [α] = -109.21 (c
D
9
5
4
1
4
8
.00, CHCl3).
.2.12. (S)-N-(o-methylbenzylidene)-2-chlorotetrafluoroethanesulfinamide (1l). Yield
-1
1
5%; Colorless oil; FT-IR (film) 1592, 1567, 1137, 803 cm ; H NMR (300 MHz, CDCl ):
3
δ 9.08 (s, 1H), 7.97 (d, J = 7.2 Hz, 1H), 7.49 (dd, J = 7.3, 0.9 Hz, 1H), 7.37−7.29 (m, 2H),
17

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3
4
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1
9
2
.63 (s, 3H); F NMR (282 MHz, CDCl ): δ -66.64 (s, 2F), -116.72 (d, J = 229.8 Hz, 1F),
3 FF
1
3
-118.06 (d, JFF = 229.8 Hz, 1F); C NMR (100 MHz, CDCl
): δ 165.8, 141.0, 133.8, 131.6,
3
+
131.3, 130.6, 126.7, 19.5; HRMS (ESI) Calcd for C
H
8
NOS [M-C
F
4
Cl] 166.0332, found
8
2
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
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6
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2
6
166.0327; [α] = -52.86 (c 2.35, CHCl3).
D
4.2.13. (S)-N-(m-methylbenzylidene)-2-chlorotetrafluoroethanesulfinamide (1m). Yield
-1 1
9
4%; Colorless oil; FT-IR (film) 1698, 1563, 785 cm ; H NMR (300 MHz, CDCl ): δ 8.78
3
19
(
s, 1H), 7.73−7.70 (m, 2H), 7.43−7.41 (m, 2H), 2.44 (s, 3H); F NMR (282 MHz, CDCl ):
3
1
3
δ -65.89 (s, 2F), -115.88 (d, J = 229.6 Hz, 1F), -117.18 (d, J = 229.6 Hz, 1F); C NMR
FF
FF
(
100 MHz, CDCl ): δ 167.3, 139.3, 135.2, 133.2, 130.8, 129.2, 128.0, 21.2; HRMS (ESI)
3
26
Calcd for C H ClF NOS 300.9951, found 300.9956; [α] = -84.68 (c 2.38, CHCl3).
1
0
8
4
D
4
9
7
.2.14. (S)-N-(p-methylbenzylidene)-2-chlorotetrafluoroethanesulfinamide (1n). Yield
8%; White solid; mp 86−88 °C; FT-IR (KBr) 1593, 1562, 1176, 1159, 1143, 1106, 817,
-1
1
88, 748 cm ; H NMR (300 MHz, CDCl ): δ 8.77 (s, 1H), 7.81 (d, J = 7.8 Hz, 2H), 7.33 (d,
3
1
9
J = 8.1 Hz, 2H), 2.45 (s, 3H); F NMR (282 MHz, CDCl ): δ -66.72 (s, 2F), -116.71 (d, J
3
FF
13
=
224.8 Hz, 1F), -118.28 (d, J = 224.8 Hz, 1F); C NMR (100 MHz, CDCl ): δ 166.6,
FF 3
1
45.5, 130.6, 130.5, 130.0, 21.9; HRMS (ESI) Calcd for C H ClF NOS 300.9951, found
10 8 4
3
00.9958; Anal. Calcd for C H ClF NOS: C, 39.81; H, 2.67; N, 4.64. Found: C, 40.06; H,
10 8 4
2
6
2.75; N, 4.63; [α]
= -112.88 (c 1.00, CHCl ).
3
D
4.2.15. (S)-N-(o-methoxybenzylidene)-2-chlorotetrafluoroethanesulfinamide (1o). Yield
-1 1
99%; White solid; mp 72−73 °C; FT-IR (KBr) 1590, 1258, 1135, 800, 761 cm ; H NMR
(300 MHz, CDCl ): δ 9.25 (s, 1H), 7.97 (d, J = 7.8 Hz, 1H), 7.50 (dd, J = 7.8, 7.8 Hz, 1H),
3
19
7
.00−6.91 (m, 2H), 3.84 (s, 3H); F NMR (282 MHz, CDCl ): δ -65.79 (s, 2F), -115.79 (d,
3
1
3
J = 230.1 Hz, 1F), -117.74 (d, J = 230.1 Hz, 1F); C NMR (100 MHz, CDCl ): δ 189.7,
FF
FF
3
1
3
4
8
62.5, 160.2, 135.8, 128.6, 120.6, 111.3, 55.3; HRMS (ESI) Calcd for C H ClF NO S
10 8 4 2
26
16.9900, found 316.9905; [α] = +31.52 (c 1.10, CHCl3).
D
.2.16. (S)-N-(p-methoxybenzylidene)-2-chlorotetrafluoroethanesulfinamide (1p). Yield
-1
1
4%; White solid; mp 83−84 °C; FT-IR (KBr) 1596, 1257, 1162, 796 cm ; H NMR (300
18

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MHz, CDCl ): δ 8.72 (s, 1H), 7.87 (d, J = 8.4 Hz, 2H), 7.01 (d, J = 8.4 Hz, 2H), 3.90 (s,
3
19
3H); F NMR (282 MHz, CDCl
): δ -66.61 (s, 2F), -117.02 (d, JFF = 232.4 Hz, 1F), -118.62
(d, JFF = 232.4 Hz, 1F); C NMR (100 MHz, CDCl ): δ 165.6, 164.6, 132.6, 126.2, 114.6,
55.6; HRMS (ESI) Calcd for C H ClF NO S 316.9900, found 316.9903; [α] = -150.51
3
1
3
3
1
1
1
1
1
1
1
1
1
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6
6
6
6
6
6
2
6
1
0
8
4
2
D
(c 1.20, CHCl3).
.2.17. (S)-N-(o-trifluoromethylbenzylidene)-2-chlorotetrafluoroethanesulfinamide
4
-1
1
(
1q). Yield 91%; Colorless oil; FT-IR (film) 1597, 1177, 1136, 769, 729 cm ; H NMR
(
300 MHz, CDCl ): δ 9.20 (s, 1H), 8.31 (dd, J = 5.3, 1.8 Hz, 1H), 7.84−7.81 (m, 1H),
3
1
9
7
.74−7.71 (m, 2H); F NMR (282 MHz, CDCl ): δ -57.15 (s, 3F), -66.72 (s, 2F), -115.74 (d,
3
13
J = 227.6 Hz, 1F), -117.10 (d, J = 227.6 Hz, 1F); C NMR (100 MHz, CDCl ): δ 163.8,
FF
FF
3
1
33.6, 132.6, 131.0 (q, J = 31.7 Hz), 123.0, 126.5 (q, J = 8.0 Hz), 125.0, 122.3 (q, J = 32.5
+
26
Hz); HRMS (ESI) Calcd for C H F NOS [M-C F Cl] 220.0044, found 220.0042; [α] =
D
8
5
3
2
4
-72.47 (c 1.01, CHCl3).
4
.2.18.
(S)-N-(m-trifluoromethylbenzylidene)-2-chlorotetrafluoroethanesulfinamide
-1 1
(
1r). Yield 95%; Colorless oil; FT-IR (film) 1613, 1588, 1011, 901, 807, 694 cm ; H NMR
(
300 MHz, CDCl ): δ 8.87 (s, 1H), 8.18 (s, 1H), 8.11 (d, J = 7.8 Hz, 1H), 7.88 (d, J = 7.2
3
19
Hz, 1H), 7.69 (dd, J = 7.8, 7.2 Hz, 1H); F NMR (282 MHz, CDCl ): δ -63.46 (s, 3F),
3
1
3
-66.79 (s, 2F), -116.19 (d, JFF = 229.6 Hz, 1F), -117.23 (d, JFF = 229.6 Hz, 1F); C NMR
(100 MHz, CDCl ): δ 166.0, 133.8, 133.4, 132.1 (q, J = 49.6 Hz), 130.6, 130.5, 127.0 (q, J
3
+
= 5.9 Hz), 124.9; HRMS (ESI) Calcd for C H F NOS [M-C F Cl] 220.0044, found
8
5
3
2 4
2
6
2
20.0050; [α] = -60.75 (c 1.00, CHCl3).
D
4
.2.19. (S)-N-(p-trifluoromethylbenzylidene)-2-chlorotetrafluoroethanesulfinamide (1s).
-1 1
Yield 82%; White solid; mp 31−32 °C; FT-IR (KBr) 1609, 1324, 797 cm ; H NMR (300
1
9
MHz, CDCl ): δ 8.87 (s, 1H), 8.05 (d, J = 8.1 Hz, 2H), 7.80 (d, J = 8.1 Hz, 2H); F NMR
3
(282 MHz, CDCl ): δ -63.01 (s, 3F), -66.07 (s, 2F), -115.25 (d, J = 228.4 Hz, 1F), -116.61
3 FF
13
(
d, J = 228.4 Hz, 1F); C NMR (100 MHz, CDCl ): δ 166.0, 135.9, 135.4 (q, J = 32.1
FF
3
+
Hz), 130.7, 126.4 (q, J = 3.6 Hz), 122.2; HRMS (ESI) Calcd for C H F NOS [M-C F Cl]
8
5
3
2 4
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20.0044, found 220.0047; [α]
D
= -66.91 (c 1.01, CHCl3).
4.2.20. (S)-N-(p-cyanobenzylidene)-2-chlorotetrafluoroethanesulfinamide (1t). Yield
-
1 1
60%; White solid; mp 79−87 °C; FT-IR (KBr) 2232, 1596, 1193, 1114, 1026, 806 cm ; H
1
1
1
1
1
1
1
1
1
1
2
2
2
2
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6
NMR (300 MHz, CDCl ): δ 8.85 (s, 1H), 8.03 (d, J = 7.8 Hz, 2H), 7.83 (d, J = 7.8 Hz, 2H);
3
1
9
F NMR (282 MHz, CDCl ): δ -66.75 (s, 2F), -115.58 (d, J = 226.7 Hz, 1F), -117.00 (d,
3
FF
13
JFF = 226.7 Hz, 1F); C NMR (100 MHz, CDCl ): δ 165.5, 136.2, 133.0, 130.6, 117.7,
3
2
6
1
17.2; HRMS (EI) Calcd for C H ClF N OS 311.9747, found 311.9749. [α] = -159.76
10 5 4 2 D
(c 0.71, CHCl3).
4
8
.2.21. (S)-N-(o-allylbenzylidene)-2-chlorotetrafluoroethanesulfinamide (1u). Yield
-1
1
2%; Colorless oil; FT-IR (film) 3080, 1607, 1590, 1184, 761 cm ; H NMR (300 MHz,
CDCl ): δ 8.98 (s, 1H), 7.94 (d, J = 7.8 Hz, 1H), 7.42 (dd, J = 7.4, 7.4 Hz, 1H), 7.29−7.20
3
(
m, 2H), 5.95−5.82 (m, 1H), 5.01 (d, J = 9.0 Hz, 1H), 4.85 (d, J = 17.1 Hz, 1H), 3.62 (d, J =
19
5
.7 Hz, 2H); F NMR (282 MHz, CDCl ): δ -65.92 (s, 2F), -116.00 (d, J = 229.6 Hz, 1F),
3
FF
1
3
-
117.09 (d, J = 229.6 Hz, 1F); C NMR (100 MHz, CDCl ): δ 165.6, 142.6, 136.5, 134.1,
FF 3
+
1
31.2, 131.1, 130.2, 127.3, 117.0, 37.0; HRMS (EI) Calcd for C H ClF NOSNa [M+Na]
12 14 4
2
6
3
50.0000, found 350.0013; [α]
= -23.87 (c 1.24, CHCl3).
D
4.2.22. (S)-N-(naphthylidene)-2-chlorotetrafluoroethanesulfinamide (1v). Yield 99%;
-
1 1
White solid; mp 43−45°C; FT-IR (KBr) 1579, 1142, 1062, 761, 699 cm ; H NMR (300
MHz, CDCl ): δ 9.36 (s, 1H), 9.01 (d, J = 8.1 Hz, 1H), 8.14−8.11 (m, 2H), 7.96 (d, J = 7.5
3
1
9
Hz, 1H), 7.71 (dt, J = 6.8, 1.4 Hz, 1H), 7.65−7.60 (m, 2H); F NMR (282 MHz, CDCl ): δ
3
13
-66.06 (s, 2F), -116.29 (d, J = 229.0 Hz, 1F), -117.18 (d, J = 229.0 Hz, 1F); C NMR
FF
FF
(
100 MHz, CDCl ): δ 166.6, 135.5, 134.3, 133.9, 131.3, 129.1, 128.9, 128.4, 127.0, 125.2,
3
2
6
1
1
4
24.1; HRMS (EI) Calcd for C H ClF NOS 336.9951, found 336.9944; [α] = -136.16 (c
13 8 4 D
.30, CHCl3).
.2.23. (S)-N-(thienylidene)-2-chlorotetrafluoroethanesulfinamide (1w). Yield 91%;
-1
1
White solid; mp 66−67 °C; FT-IR (KBr) 1578, 1423, 1267, 800 cm ; H NMR (300 MHz,
19
CDCl ): δ 8.89 (s, 1H), 7.77−7.71 (m, 2H), 7.22 (s, 1H); F NMR (282 MHz, CDCl ): δ
3
3
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66.02 (s, 2F), -116.20 (d, J = 229.7 Hz, 1F), -117.32 (d, J = 229.7 Hz, 1F); C NMR
FF FF
(100 MHz, CDCl
): δ 159.2, 139.4, 136.9, 135.7, 128.8; HRMS (ESI) Calcd for
3
2
6
C
H
4
ClF
NOS 292.9359, found 292.9362; [α] = -245.09 (c 1.1450, CHCl ).
4 2 D 3
7
1
1
1
1
1
1
1
1
1
1
2
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4.2.24. 2-Chloro-N-(3-methylbutylidene)tetrafluoroethanesulfinamide (1x). Yield 87%;
-1
1
Colorless oil; FT-IR (film) 2964, 2876, 1620, 1390, 1371 cm ; H NMR (300 MHz,
CDCl ): δ 8.29 (t, J = 5.4 Hz), 2.53−2.38 (m, 2H), 2.13−1.99 (m, 1H), 0.95 (d, J = 3.0 Hz,
3
1
9
3
H), 0.92 (d, J = 2.7 Hz, 3H); F NMR (282 MHz, CDCl ): δ -66.36 (s, 2F), -117.22 (d, J
3 FF
13
=
230.7 Hz, 1F), -117.73 (d, J = 230.7 Hz, 1F); C NMR (100 MHz, CDCl ): δ 175.4,
FF 3
1
22.2 (tt, J = 299.2, 33.1 Hz), 116.5 (tt, J = 272.5, 36.5 Hz), 45.3, 26.0, 22.4, 22.3; HRMS
+
(ESI) Calcd for C H ClF NOS [M+H] 268.0186, found 268.0181.
7
11
4
4.2.25. 2-Chloro-N-(2,2-dimethylpropylidene)tetrafluoroethanesulfinamide (1y). Yield
-1
1
8
5%; Colorless oil; FT-IR (film) 1717, 1618, 1404, 1266 cm ; H NMR (300 MHz,
19
CDCl ): δ 8.15 (s, 1H), 1.08 (s, 9H); F NMR (282 MHz, CDCl ): δ -65.72 (s, 2F), -116.29
3
3
13
(
d, J = 234.6 Hz, 1F), -118.29 (d, J = 234.6 Hz, 1F); C NMR (100 MHz, CDCl ): δ
FF FF 3
1
81.3, 122.4 (tt, J = 298.5, 32.7 Hz), 116.8 (tt, J = 301.4, 36.5 Hz), 39.1, 26.3; HRMS (ESI)
+
Calcd for C H ClF NOS [M+H] 268.0181, found 268.0186.
7
11
4
4
.3. General procedure for the AVM reaction in DMSO
To a 10 mL round-bottomed flask equipped with a magnetic stir bar was placed imine 1
(
0.5 mmol), followed by the addition of DMSO (1.0 mL). Then 2a (1.0 mmol) was added
19
dropwise. The mixture was stirred at room temperature and monitored by F NMR spectra.
After disappearance of 1, ethyl acetate (5.0 mL) and water (2.0 mL) was added. The
aqueous phase was extracted with EtOAc (2.0 mL×3). The combined organic phase was
washed with water (1.0 mL×4), dried over anhydrous Na
reduced pressure. Flash column chromatography (DCM/EtOAc: 30/1) gave the product.
4.3.1. (Ss,4R,5R)-[(p-chlorophenyl)(2-chlorotetrafluoroethanesulfinylamino)methyl]
furan-2(5H)-one (3a). White solid; mp 145−146 °C; FT-IR (KBr) 3167, 1758, 815, 788
SO and concentrated under
2
4
-1 1
cm ; H NMR (300 MHz, CDCl ): δ 7.48 (d, J = 5.7 Hz, 1H), 7.36 (d, J = 8.7 Hz, 2H), 7.32
3
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(
d, J = 8.7 Hz, 2H), 6.38 (dd, J = 5.6, 1.1 Hz, 1H), 6.26 (d, J = 5.6 Hz, 1H), 5.30 (s, 1H),
1
9
5.03 (dd, J = 8.7, 2.4 Hz, 1H); F NMR (282 MHz, CDCl ): δ -66.83 (s, 2F), -112.03 (d,
3
1
3
J
FF = 233.8 Hz, 1F), -121.98 (d, JFF = 233.8 Hz, 1F); C NMR (100 MHz, CDCl ): δ 173.0,
3
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
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3
3
3
3
3
3
3
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4
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5
5
5
6
6
6
6
6
6
+
154.5, 135.5, 134.9, 129.4, 128.7, 123.7, 86.1, 54.1; MS (ESI) 423 [M+NH ] ; Anal. Calcd
4
2
6
for C H Cl F NO S: C, 38.44; H, 2.23; N, 3.45. Found C, 38.57; H, 1.97; N, 3.53; [α] =
D
13
9
2
4
3
-52.41 (c 1.00, CHCl ); Crystal data: C H Cl F NO S; M = 406.17; Monoclinic, C2/c; a =
3 13 9 2 4 3
2
8
6.411 (3) Å, b = 10.8260 (11) Å, c = 12.8480 (13) Å; α = 90, β = 116.807 (2), γ = 90; Z = 8;
726 reflections; R = 0.0213, R = 0.0497, wR = 0.1269. Crystallographic data for the
int
1
2
structures of 3a have been deposited with the Cambridge Crystallographic Data Centre
CCDC 211108).
.3.2. (Ss,4R,5R)-[(phenyl)(2-chlorotetrafluoroethanesulfinylamino)methyl]furan
2(5H)-one (3b). White solid; mp 128−129 °C; FT-IR (KBr) 3226, 1747, 1602, 1178, 1122,
(
4
-
-1
1
7
67, 701 cm ; H NMR (300 MHz, d -DMSO): δ 8.73 (d, J = 7.4 Hz, 1H), 7.56 (d, J = 7.4
6
Hz, 1H), 7.46−7.32 (m, 5H), 6.31 (d, J = 5.9 Hz, 1H), 5.38 (s, 1H), 5.16 (d, J = 5.9 Hz, 1H);
1
9
F NMR (282 MHz, d -DMSO): δ -66.95 (s, 2F), -111.27 (d, J = 234.6 Hz, 1F), -122.53
6
FF
13
(d, JFF = 234.6 Hz, 1F); C NMR (100 MHz, d -DMSO): δ 172.4, 155.5, 137.8, 128.2,
6
+
1
27.8, 127.4, 122.3, 85.6, 54.2; MS (ESI) 389 [M+NH ] ; Anal. Calcd for
4
2
6
C H ClF NO S: C, 42.00; H, 2.71; N, 3.77. Found C, 42.25; H, 2.85; N, 3.57; [α] =
D
13
10
4
3
-21.41 (c 0.95, CHCl3).
4
.3.3.
(Ss,4R,5R)-[(o-chlorophenyl)(2-chlorotetrafluoroethanesulfinylamino)methyl]
furan-2(5H)-one (3c). White solid; mp 134−136 °C; FT-IR (KBr) 3168, 1748, 1600, 1174,
-1 1
1113, 789, 751 cm ; H NMR (300 MHz, d
-DMSO): δ 8.99 (d, J = 7.4 Hz, 1H), 7.65 (d, J
6
= 7.4 Hz, 1H), 7.57−7.39 (m, 4H), 6.40 (d, J = 3.9 Hz, 1H), 5.44 (d, J = 3.9 Hz, 1H), 5.38 (s,
19
1H); F NMR (282 MHz, d -DMSO): δ -63.20 (s, 2F), -107.73 (d, J = 233.5 Hz, 1F),
6
FF
13
-119.49 (d, J = 233.5 Hz, 1F); C NMR (100 MHz, CDCl ): δ 173.5, 155.2, 134.8, 132.0,
FF
3
+
1
29.8, 129.7, 129.3, 127.7, 123.5, 84.9, 50.3; MS (ESI) 423 [M+NH ] ; Anal. Calcd for
4
2
6
C H Cl F NO S: C, 38.44; H, 2.23; N, 3.45. Found C, 38.71; H, 2.38; N, 3.47; [α] =
D
13
9
2
4
3
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4
5
+
6.84 (c 0.93, CHCl3).
4.3.4. (Ss,4R,5R)-[(m-chlorophenyl)(2-chlorotetrafluoroethanesulfinylamino)methyl]
furan-2(5H)-one (3d). White solid; mp 138−139 °C; FT-IR (KBr) 3173, 1754, 1455, 1256,
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
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3
3
3
4
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5
5
5
5
5
5
5
5
5
6
6
6
6
6
6
-
1 1
1181, 787, 691, 613 cm ; H NMR (300 MHz, d -DMSO): δ 8.77 (d, J = 9.9 Hz, 1H), 7.56
6
1
9
(s, 2H), 7.43 (s, 3H), 6.35 (d, J = 4.5 Hz, 1H), 5.40 (s, 1H), 5.26 (d, J = 4.5 Hz, 1H); F
NMR (282 MHz, d -DMSO): δ -66.95 (s, 2F), -111.22 (d, J = 233.5 Hz, 1F), -122.53 (d,
6
FF
1
3
JFF = 233.5 Hz, 1F); C NMR (100 MHz, CDCl ): δ 172.9, 154.4, 139.0, 135.1, 130.4,
3
+
1
29.1, 127.5, 125.5, 123.7, 86.0, 54.3; MS (ESI) 423 [M+NH ] ; Anal. Calcd for
4
C H Cl F NO S: C, 38.44; H, 2.23; N, 3.45; F, 18.71. Found C, 38.58; H, 2.36; N, 3.48; F,
13
9
2
4
3
26
1
8.85; [α] = -28.76 (c 1.00, CHCl3).
D
4
.3.5. (Ss,4R,5R)-[(2,4-dichlorophenyl)(2-chlorotetrafluoroethanesulfinylamino)methyl]
furan-2-(5H)-one (3e). White solid; mp 136−138 °C; FT-IR (KBr) 3171, 1748, 1471, 1258,
-1
1
8
7
15, 791cm ; H NMR (300 MHz, d -DMSO): δ 9.01 (d, J = 9.3 Hz, 1H), 7.71 (s, 1H),
6
.67 (d, J = 5.4 Hz, 1H), 7.60 (d, J = 9.0 Hz, 1H), 7.55 (d, J = 9.0 Hz, 1H), 6.41 (d, J = 4.5
1
9
Hz, 1H), 5.42 (dd, J = 9.2, 2.9 Hz, 1H), 5.38 (s, 1H); F NMR (282 MHz, d -DMSO): δ
6
1
3
-67.02 (s, 2F), -111.58 (d, J = 233.8 Hz, 1F), -123.30 (d, J = 233.8 Hz, 1F); C NMR
FF FF
(100 MHz, CDCl ): δ 173.5, 155.1, 135.3, 133.5, 132.6, 130.3, 129.5, 127.9, 123.6, 84.7,
3
+
49.5; MS (ESI) 457 [M+NH
] ; Anal. Calcd for C13
H
8
Cl
F
4
NO
S: C, 35.44; H, 1.83; N,
4
3
3
2
6
3.18; F, 17.25. Found: C, 35.61; H, 2.04; N, 2.92; F, 17.47; [α] = -12.98 (c 1.05, CHCl3).
D
4.3.6.
(Ss,4R,5R)-[(o-fluorophenyl)(2-chlorotetrafluoroethanesulfinylamino)methyl]
furan-2(5H)-one (3f). White solid; mp 129−130 °C; FT-IR (KBr) 3287, 1748, 1493, 1180,
-1 1
7
58, 681 cm ; H NMR (300 MHz, d -DMSO): δ 8.90 (d, J = 9.0 Hz, 1H), 7.67 (d, J = 5.4
6
Hz, 1H), 7.51 (dd, J = 7.4, 7.4 Hz, 1H), 7.41 (dd, J = 12.9, 6.3 Hz, 1H), 7.29 (d, J = 6.3 Hz,
1
H), 7.24 (d, J = 7.4 Hz, 1H), 6.37 (d, J = 5.1 Hz, 1H), 5.38 (s, 1H), 5.35 (d, J = 9.0 Hz,
19
1
H); F NMR (282 MHz, d -DMSO): δ -66.99 (s, 2F), -111.75 (d, J = 233.8 Hz, 1F),
6
FF
13
-117.52 (s, 1F), -122.58 (d, JFF = 233.8 Hz, 1F); C NMR (100 MHz, CDCl ): δ 173.1,
3
1
59.7 (d, J = 244.9 Hz), 154.5, 130.5 (d, J = 8.1 Hz), 129.1 (d, J = 2.9 Hz), 125.0 (d, J = 2.9
23

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Hz), 124.2 (d, J = 13.2 Hz), 123.6, 115.7 (d, J = 21.1 Hz), 85.3, 48.9; MS (ESI) 407
+
[M+NH
] ; Anal. Calcd for C13
H
9
ClF
NO
S: C, 40.06; H, 2.33; N, 3.59; F, 24.37. Found C,
4
5
3
2
6
39.93; H, 2.49; N, 3.60; F, 24.27; [α]
4.3.7. (Ss,4R,5R)-[(m-fluorophenyl)(2-chlorotetrafluoroethanesulfinylamino)methyl]
furan-2(5H)-one (3g). White solid; mp 142−143 °C; FT-IR (KBr) 3265, 1758, 1492, 1180,
= -14.88 (c 1.18, CHCl ).
D
3
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
6
6
6
6
6
-1 1
7
90, 696 cm ; H NMR (300 MHz, d -DMSO): δ 8.76 (d, J = 9.9 Hz, 1H), 7.56 (d, J = 5.4
6
Hz, 1H), 7.45 (dd, J = 14.3, 7.4 Hz, 1H), 7.32−7.29 (m, 2H), 7.16 (dd, J = 8.3, 8.3 Hz, 1H),
1
9
6
.34 (d, J = 5.4 Hz, 1H), 5.40 (s, 1H), 5.25 (d, J = 9.9 Hz, 1H); F NMR (282 MHz,
d -DMSO): δ -66.95 (s, 2F), -111.33 (d, J = 233.8 Hz, 1F), -112.67 to -112.76 (m, 1F),
6
FF
13
-
122.50 (d, J = 233.8 Hz, 1F); C NMR (100 MHz, CDCl ): δ 173.1, 163.0 (d, J = 245.7
F
F
3
Hz), 154.7, 139.6 (d, J = 7.3 Hz), 130.7 (d, J = 8.1 Hz), 123.6, 122.9 (d, J = 2.9 Hz), 115.8
+
(
d, J = 20.4 Hz), 114.5 (d, J = 22.6 Hz), 86.2, 54.0; MS (ESI) 407 [M+NH ] ; Anal. Calcd
4
for C H ClF NO S: C, 40.06; H, 2.33; N, 3.59; F, 24.37. Found C, 40.00; H, 2.41; N, 3.43;
1
3
9
5
3
2
6
F, 24.39; [α] = -23.28 (c 1.00, CHCl3).
D
4
.3.8.
(Ss,4R,5R)-[(p-fluorophenyl)(2-chlorotetrafluoroethanesulfinylamino)methyl]
furan-2(5H)-one (3h). White solid; mp 147−149 °C; FT-IR (KBr) 3287, 1745, 1605, 1178,
-1 1
1
119, 792, 680 cm ; H NMR (300 MHz, d -DMSO): δ 8.75 (d, J = 9.3 Hz, 1H), 7.53−7.49
6
(m, 3H), 7.23 (dd, J = 7.5, 7.5 Hz, 2H), 6.32 (d, J = 3.3 Hz, 1H), 5.36 (s, 1H), 5.20 (d, J =
1
9
7.5 Hz, 1H); F NMR (282 MHz, d -DMSO): δ -66.96 (s, 2F), -111.38 (d, J = 233.5 Hz,
6
FF
1
3
1F), -114.22 (s, 1F), -123.25 (d, J = 233.5 Hz, 1F); C NMR (100 MHz, d -DMSO): δ
FF
6
172.3, 161.7 (d, J = 242.1 Hz), 155.4, 134.1 (d, J = 2.9 Hz), 129.6 (d, J = 8.8 Hz), 122.5,
+
1
15.1 (d, J = 21.8 Hz), 85.5, 53.5; MS (ESI) 407 [M+NH ] ; Anal. Calcd for
4
C H ClF NO S: C, 40.06; H, 2.33; N, 3.59; F, 24.37. Found C, 39.99; H, 2.31; N, 3.46; F,
13
9
5
3
26
2
4.76; [α] = -19.99 (c 1.18, CHCl3).
D
4
.3.9.
(Ss,4R,5R)-[(o-bromophenyl)(2-chlorotetrafluoroethanesulfinylamino)methyl]
furan-2(5H)-one (3i). White solid; mp 173−174 °C; FT-IR (KBr) 3258, 1750, 1605, 1441,
-1
1
1
262, 758, 734 cm ; H NMR (300 MHz, d -DMSO): δ 9.00 (d, J = 9.3 Hz, 1H), 7.69−7.63
6
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(
m, 2H), 7.56−7.47 (m, 2H), 7.31 (dd, J = 6.6, 6.6 Hz, 1H), 6.41 (d, J = 4.5 Hz, 1H), 5.42 (d,
19
J = 9.6 Hz, 1H), 5.37 (s, 1H); F NMR (282 MHz, d -DMSO): δ -67.05 (s, 2F), -111.56 (d,
6
13
J
FF = 234.6 Hz, 1F), -123.29 (d, JFF = 234.6 Hz, 1F); C NMR (100 MHz, CDCl
): δ 173.5,
3
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
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4
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6
6
6
6
6
+
155.2, 136.4, 133.0, 130.1, 129.5, 128.3, 123.5, 122.3, 85.0, 52.5; MS (ESI) 467 [M+NH ] ;
4
Anal. Calcd for C H BrClF NO S: C, 34.65; H, 2.01; N, 3.11; F, 16.86. Found C, 34.48; H,
13
9
4
3
2
6
2
.16; N, 3.10; F, 16.66; [α] = +3.74 (c 1.00, CHCl3).
D
4
.3.10. (Ss,4R,5R)-[(m-bromophenyl)(2-chlorotetrafluoroethanesulfinylamino)methyl]
furan-2(5H)-one (3j). White solid; mp 138−139 °C; FT-IR (KBr) 3167, 1752, 1181, 786,
-1
1
6
7
1
93 cm ; H NMR (300 MHz, d -DMSO): δ 8.76 (d, J = 9.9 Hz, 1H), 7.70 (s, 1H),
6
.56−7.53 (m, 2H), 7.47 (d, J = 7.5 Hz, 1H), 7.37 (dd, J = 7.8, 7.8 Hz, 1H), 6.35 (dd, J = 4.2,
19
.2 Hz, 1H), 5.39 (s, 1H), 5.24 (dd, J = 6.6, 4.5 Hz, 1H); F NMR (282 MHz, d -DMSO): δ
6
13
-67.02 (s, 2F), -111.16 (d, J = 233.8 Hz, 1F), -122.49 (d, J = 233.8 Hz, 1F); C NMR
FF
FF
(100 MHz, CDCl ): δ 172.9, 154.4, 139.2, 132.1, 130.7, 130.4, 126.0, 123.8, 122.2, 85.9,
3
+
5
4.5; HRMS (ESI) calcd for C H BrClF NO SNa [M+Na] 471.9003, found 471.8998;
13
9
4
3
2
6
[
α]
D
= -29.74 (c 1.00, CHCl3).
4
.3.11. (Ss,4R,5R)-[(p-bromophenyl)(2-chlorotetrafluoroethanesulfinylamino)methyl]
furan-2(5H)-one (3k). White solid; mp 156−158 °C; FT-IR (KBr) 3177, 1752, 1602, 1179,
-1 1
813, 706 cm ; H NMR (300 MHz, d
-DMSO): δ 8.75 (d, J = 9.9 Hz, 1H), 7.61 (d, J = 8.1
6
Hz, 2H), 7.56 (d, J = 5.1 Hz, 1H), 7.40 (d, J = 8.1 Hz, 2H), 6.34 (d, J = 4.5 Hz, 1H), 5.36 (s,
19
1H), 5.21 (d, J = 9.0 Hz, 1H); F NMR (282 MHz, d -DMSO): δ -67.31 (s, 2F), -111.55 (d,
6
13
J = 233.5 Hz, 1F), -122.88 (d, J = 233.5 Hz, 1F); C NMR (100 MHz, d -DMSO): δ
FF
FF
6
+
1
72.3, 155.3, 137.3, 131.2, 129.6, 122.5, 121.1, 85.3, 53.4; MS (ESI) 467 [M+NH ] ; Anal.
4
Calcd for C H BrClF NO S: C, 34.65; H, 2.01; N, 3.11; F, 16.86. Found C, 34.62; H, 2.11;
13
9
4
3
26
N, 3.17; F, 16.95; [α] = -52.74 (c 1.00, CHCl3).
D
4
.3.12. (Ss,4R,5R)-[(o-methylphenyl)(2-chlorotetrafluoroethanesulfinylamino)methyl]
furan-2-(5H)-one (3l). White solid; mp 107−108 °C; FT-IR (KBr) 3276, 1744, 1606, 1183,
-1
1
7
30 cm ; H NMR (300 MHz, d -DMSO): δ 8.77 (d, J = 9.3 Hz, 1H), 7.62 (d, J = 5.4 Hz,
6
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H), 7.41 (d, J = 5.7 Hz, 1H), 7.25−7.22 (m, 3H), 6.33 (d, J = 5.1 Hz, 1H), 5.35 (s, 1H),
19
5.20 (dd, J = 9.2, 3.5 Hz, 1H), 2.34 (s, 3H); F NMR (282 MHz, d -DMSO): δ -66.89 (s,
6
1
3
2F), -111.63 (d, JFF = 234.6 Hz, 1F), -123.20 (d, JFF = 234.6 Hz, 1F); C NMR (100 MHz,
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
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3
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3
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3
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3
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4
4
4
4
5
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5
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5
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5
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5
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6
6
6
6
CDCl ): δ 172.8, 154.1, 135.1, 134.3, 131.2, 129.0, 127.3, 127.0, 123.7, 85.5, 52.7, 19.4;
3
+
26
HRMS (ESI) calcd for C H ClF NO SNa [M+Na] 408.0055, found 408.0059; [α] =
D
14
12
4
3
+
20.18 (c 1.80, CHCl3).
.3.13. (Ss,4R,5R)-[(m-methylphenyl)(2-chlorotetrafluoroethanesulfinylamino)methyl]
furan-2-(5H)-one (3m). White solid; mp 123−125 °C; FT-IR (KBr) 3265, 1748, 793, 689
4
-1 1
cm ; H NMR (300 MHz, d -DMSO): δ 8.68 (d, J = 9.6 Hz, 1H), 7.54 (d, J = 5.4 Hz, 1H),
6
7
.30−7.22 (m, 3H), 7.14 (d, J = 6.9 Hz, 1H), 6.30 (d, J = 5.4 Hz, 1H), 5.36 (s, 1H), 5.09 (d,
19
J = 9.0 Hz, 1H), 2.32 (s, 3H); F NMR (282 MHz, d -DMSO): δ -66.78 (s, 2F), -110.95 (d,
6
13
J = 233.5 Hz, 1F), -122.50 (d, J = 233.5 Hz, 1F); C NMR (100 MHz, CDCl ): δ 173.0,
FF
FF
3
1
54.4, 139.0, 136.5, 129.3, 129.0, 127.9, 124.3, 123.5, 86.2, 56.3, 21.4; HRMS (ESI) calcd
+
26
for C H ClF NO SNa [M+Na] 408.0055, found 408.0065; [α] = -11.35 (c 1.56,
D
1
4
12
4
3
CHCl3).
4
.3.14. (Ss,4R,5R)-[(p-methylphenyl)(2-chlorotetrafluoroethanesulfinylamino)methyl]
furan-2-(5H)-one (3n). White solid; mp 108−109 °C; FT-IR (KBr) 3211, 1747, 1178, 1071,
-1 1
815, 791 cm ; H NMR (300 MHz, d
-DMSO): δ 8.67 (d, J = 9.6 Hz, 1H), 7.55 (d, J = 5.4
6
Hz, 1H), 7.31 (d, J = 7.5 Hz, 2H), 7.19 (d, J = 7.5 Hz, 2H), 6.29 (d, J = 5.1 Hz, 1H), 5.34 (s,
19
1H), 5.08 (d, J = 8.3 Hz, 1H), 2.30 (s, 3H); F NMR (282 MHz, d -DMSO): δ -66.83 (s,
6
1
3
2F), -111.19 (d, J = 233.8 Hz, 1F), -122.41 (d, J = 233.8 Hz, 1F); C NMR (100 MHz,
FF
FF
CDCl ): δ 172.6, 154.0, 139.1, 133.4, 130.0, 127.3, 123.6, 86.0, 57.0, 21.3; MS (ESI) 403
3
+
[
M+NH ] ; Anal. Calcd for C H ClF NO S: C, 43.59; H, 3.14; N, 3.63; F, 19.70. Found C,
4
14 12
4
3
26
4
4
3.81; H, 3.26; N, 3.36; F, 19.51; [α] = -26.87 (c 1.22, CHCl3).
D
.3.15. (Ss,4R,5R)-[(o-methoxyphenyl)(2-chlorotetrafluoroethanesulfinylamino)methyl]
furan-2-(5H)-one (3o). White solid; mp 84−86 °C; FT-IR (KBr) 3176, 1761, 1494, 1245,
-1
1
1182, 804, 764 cm ; H NMR (300 MHz, d -DMSO): δ 8.65 (d, J = 9.9 Hz, 1H), 7.56 (d, J
6
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=
5.4 Hz, 1H), 7.40−7.31 (m, 2H), 7.08−6.98 (m, 2H), 6.33 (d, J = 5.4 Hz, 1H), 5.33 (d, J =
1
9
7.2 Hz, 1H), 5.31 (s, 1H), 3.84 (s, 3H); F NMR (282 MHz, d -DMSO): δ -66.86 (s, 2F),
6
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-111.27 (d, JFF = 234.6 Hz, 1F), -123.16 (d, JFF = 234.6 Hz, 1F); C NMR (100 MHz,
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CDCl ): δ 173.0 (d, J = 7.3 Hz), 156.1, 154.5 (d, J = 8.0 Hz), 130.0 (d, J = 4.4 Hz), 128.6,
3
124.7 (d, J = 4.4 Hz), 123.0 (d, J = 2.9 Hz), 121.3, 110.9, 85.0, 60.5, 55.6; HRMS (ESI)
+
26
calcd for C H ClF NO SNa [M+Na] 424.0004, found 423.9996; [α] = +11.94 (c 1.00,
14
12
4
4
D
CHCl3).
.3.16. (Ss,4R,5R)-[(p-methoxyphenyl)(2-chlorotetrafluoroethanesulfinylamino)methyl]
furan-2-(5H)-one (3p). White solid; mp 124−126 °C; FT-IR (KBr) 3205, 1747, 1611, 1258,
4
-1
1
1167, 824, 653 cm ; H NMR (300 MHz, d -DMSO): δ 8.64 (d, J = 9.6 Hz, 1H), 7.54 (d, J
6
=
5.4 Hz, 1H), 7.34 (d, J = 8.1 Hz, 2H), 6.94 (d, J = 8.1 Hz, 2H), 6.29 (d, J = 4.8 Hz, 1H),
19
5
.32 (s, 1H), 5.05 (dd, J = 9.0, 3.0 Hz, 1H), 3.76 (s, 3H); F NMR (282 MHz, d -DMSO): δ
6
13
-
(
(
66.85 (s, 2F), -111.37 (d, J = 233.5 Hz, 1F), -122.25 (d, J = 233.5 Hz, 1F); C NMR
FF
FF
100 MHz, CDCl ): δ 172.5, 160.3, 153.8, 128.8, 128.2, 123.7, 114.8, 85.9, 57.2, 55.5; MS
3
+
ESI) 419 [M+NH ] ; Anal. Calcd for C H ClF NO S: C, 41.85; H, 3.01; N, 3.49; F, 18.92.
4
14 12
4
4
2
6
Found C, 42.05; H, 3.11; N, 3.19; F, 18.96; [α]
= -27.08 (c 1.21, CHCl3).
D
4.3.17. (Ss,4R,5S)-[(o-trifluoromethylphenyl)(2-chlorotetrafluoroethanesulfinylamino)
methyl]furan-2(5H)-one (3q). White solid; mp 169−170 °C; FT-IR (KBr) 3266, 1754, 796,
-1 1
698 cm ; H NMR (300 MHz, d -DMSO): δ 8.93 (d, J = 9.0 Hz, 1H), 7.83−7.77 (m, 3H),
6
1
9
7.62−7.57 (m, 2H), 6.41 (d, J = 5.7 Hz, 1H), 5.34 (s, 1H), 5.27 (d, J = 8.7 Hz, 1H); F
NMR (282 MHz, d -DMSO): δ -56.14 (s, 3F), -67.09 (s, 2F), -112.36 (d, J = 234.6 Hz,
6
FF
13
1
1
F), -122.26 (d, J = 234.6 Hz, 1F); C NMR (100 MHz, CDCl ): δ 173.5, 155.1, 136.3,
FF 3
32.8, 129.9, 128.6, 126.3 (q, J = 8.8 Hz), 123.6, 86.0, 49.1; HRMS (ESI) calcd for
+
26
C H ClF NO SNa [M+Na] 461.9772, found 461.9785; [α] = +9.96 (c 0.98, CHCl3).
14
9
7
3
D
4
.3.18. (Ss,4R,5S)-[(m-trifluoromethylphenyl)(2-chlorotetrafluoroethanesulfinylamino)
methyl]furan-2(5H)-one (3r). White solid; mp 153−154 °C; FT-IR (KBr) 3157, 1751, 792,
-1
1
7
03 cm ; H NMR (300 MHz, d -DMSO): δ 8.84 (d, J = 9.9 Hz, 1H), 7.85 (s, 1H),
6
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.79−7.63 (m, 3H), 7.58 (d, J = 5.7 Hz, 1H), 6.35 (d, J = 5.1 Hz, 1H), 5.44 (s, 1H), 5.38 (d,
19
J = 10.5 Hz, 1H); F NMR (282 MHz, d
-DMSO): δ -60.65 (s, 3F), -66.96 (s, 2F), -111.52
6
1
3
(d, JFF = 233.5 Hz, 1F), -122.34 (d, JFF = 233.5 Hz, 1F); C NMR (100 MHz, CDCl
): δ
3
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1
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1
1
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1
1
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2
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2
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2
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173.1, 154.6, 138.3, 131.5 (q, J = 20.4 Hz), 130.7, 130.1, 129.6, 125.6 (q, J = 5.5 Hz), 124.1,
+
123.8, 86.0, 53.7; HRMS (ESI) calcd for C H ClF NO SNa [M+Na] 461.9772, found
14
9
7
3
2
6
4
61.9783; [α] = -7.79 (c 1.50, CHCl3).
D
4
.3.19. (Ss,4R,5R)-[(p-trifluoromethylphenyl)(2-chlorotetrafluoroethanesulfinylamino)
methyl]furan-2(5H)-one (3s). White solid; mp 170−172 °C; FT-IR (KBr) 3267, 1763, 1329,
-1 1
7
90, 716 cm ; H NMR (400 MHz, d -DMSO): δ 8.85 (d, J = 10.0 Hz, 1H), 7.80 (d, J = 8.0
6
Hz, 2H), 7.69 (d, J = 8.0 Hz, 2H), 7.59 (d, J = 5.2 Hz, 1H), 6.35 (d, J = 4.4 Hz, 1H), 5.42 (s,
19
1
2
H), 5.37 (d, J = 10.0 Hz, 1H); F NMR (282 MHz, d -DMSO): δ -61.65 (s, 3F), -66.05 (s,
6
13
F), -110.81 (d, J = 231.8 Hz, 1F), -121.49 (d, J = 231.8 Hz, 1F); C NMR (100 MHz,
FF
FF
CDCl ): δ 172.6, 154.3, 141.0, 131.3 (q, J = 34.0 Hz), 127.8, 126.2 (q, J = 3.6 Hz), 123.9,
3
+
8
3
4
5.7, 54.2; MS (ESI) 457 [M+NH ] ; Anal. Calcd for C H ClF NO S: C, 38.24; H, 2.06; N,
4
14
9
7
3
2
6
.19. Found C, 38.44; H, 2.29; N, 2.90; [α]
= -28.80 (c 0.99, CHCl3).
D
.3.20. (Ss,4R,5R)-[(p-cyanophenyl)(2-chlorotetrafluoroethanesulfinylamino)methyl]
furan-2(5H)-one (3t). White solid; mp 178−176 °C; FT-IR (KBr) 3244, 2231, 1755, 1180,
-1 1
821, 786 cm ; H NMR (300 MHz, d
-acetone): δ 7.60 (d, J = 7.2 Hz, 2H), 7.42 (d, J = 7.2
6
Hz, 2H), 7.32 (d, J = 5.4 Hz, 1H), 6.51 (d, J = 9.6 Hz, 1H), 6.05 (d, J = 5.4 Hz, 1H), 5.14 (s,
1
9
1H), 5.08 (d, J = 9.9 Hz, 1H); F NMR (282 MHz, d -acetone): δ -67.37 (s, 2F), -111.54 (d,
6
13
J = 233.8 Hz, 1F), -122.98 (d, J = 233.8 Hz, 1F); C NMR (100 MHz, d -acetone): δ
FF
FF
6
+
1
84.0, 172.8, 162.1, 157.8, 152.6, 147.9, 146.9, 141.4, 114.7, 83.8; MS (ESI) 419 [M+Na] ;
Anal. Calcd for C H ClF N O S: C, 42.38; H, 2.29; N, 7.06; F, 19.15. Found C, 42.31; H,
1
4
9
4
2
3
26
2
.26; N, 6.96; F, 19.29; [α] = -82.36 (c 1.23, CHCl3).
D
4
.3.21.
(Ss,4R,5R)-[(2-allylphenyl)(2-chlorotetrafluoroethanesulfinylamino)methyl]
furan-2(5H)-one (3u). White solid; mp 102−103 °C; FT-IR (KBr) 3275, 1751, 1601, 1176,
-1
1
9
21, 767, 680 cm ; H NMR (300 MHz, d -DMSO): δ 8.68 (d, J = 9.3 Hz, 1H), 7.62 (dd, J
6
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5.7, 1.2 Hz, 1H), 7.48 (dd, J = 5.0, 3.8 Hz, 1H), 7.31−7.28 (m, 2H), 7.21 (dd, J = 5.4, 3.6
Hz, 1H), 6.33 (dd, J = 5.7, 1.8 Hz, 1H), 6.02−5.89 (m, 1H), 5.34 (d, J = 1.5 Hz, 1H), 5.24
(dd, J = 9.3, 3.8 Hz, 1H), 5.10 (d, J = 1.2 Hz, 1H), 5.05 (d, J = 8.4 Hz, 1H), 3.47 (d, J = 5.7
1
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Hz, 2H); F NMR (282 MHz, d -DMSO): δ -67.25 (s, 2F), -111.98 (d, J = 233.5 Hz, 1F),
6
FF
1
3
-122.95 (d, J = 233.5 Hz, 1F); C NMR (100 MHz, CDCl ): δ 172.8, 154.1, 136.8, 136.7,
FF
3
+
1
34.8, 130.9, 129.1, 127.8, 127.6, 123.6, 117.0, 85.8, 52.2, 37.2; MS (ESI) 434 [M+Na] ;
Anal. Calcd for C H ClF NO S: C, 46.67; H, 3.43; N, 3.40. Found C, 46.47; H, 3.33; N,
16
14
4
3
2
6
3
4
2
7
1
3
.67; [α] = +0.63 (c 1.86, CHCl3).
D
.3.22. (Ss,4R,5R)-[(naphthyl)(2-chlorotetrafluoroethanesulfinylamino)methyl] furan-
(5H)-one (3v). White solid; mp 158−159 °C; FT-IR (KBr) 3168, 1747, 1600, 1253, 1179,
-1
1
93 cm ; H NMR (300 MHz, d -DMSO): δ 8.91 (d, J = 9.6 Hz, 1H), 8.30 (d, J = 8.4 Hz,
6
H), 8.01 (d, J = 7.8 Hz, 1H), 7.95 (d, J = 7.8 Hz, 1H), 7.72−7.69 (m, 2H), 7.63−7.58 (m,
19
H), 6.35 (d, J = 5.7 Hz, 1H), 5.95 (d, J = 8.4 Hz, 1H), 5.45 (s, 1H); F NMR (282 MHz,
d -DMSO): δ -66.92 (s, 2F), -111.06 (d, J = 232.7 Hz, 1F), -123.38 (d, J = 232.7 Hz, 1F);
6
FF
FF
1
3
C NMR (100 MHz, d -DMSO): δ 172.4, 155.9, 133.7, 133.2, 129.7, 128.9, 128.5, 126.7,
6
+
1
25.8, 125.2, 122.8, 122.2, 84.8, 49.8; MS (ESI) 439 [M+NH ] ; Anal. Calcd for
4
2
6
C
H12ClF
NO
S: C, 48.41; H, 2.87; N, 3.32. Found C, 48.22; H, 2.86; N, 3.15; [α]
).
(Ss,4R,5R)-[(thienyl)(2-chlorotetrafluoroethanesulfinylamino)methyl]furan
-2(5H)-one (3w). White solid; mp 110−111 °C; FT-IR (KBr) 3182, 1735, 1269, 1116, 796,
=
17
4
3
D
+16.76 (c 1.09, CHCl
3
4.3.23.
-1 1
709 cm ; H NMR (400 MHz, d -DMSO): δ 8.72 (d, J = 9.6 Hz, 1H), 7.58 (dd, J = 5.9, 1.1
6
Hz, 1H), 7.52 (dd, J = 5.1, 1.2 Hz, 1H), 7.16 (d, J = 3.0 Hz, 1H), 7.03 (dd, J = 4.8, 3.6 Hz,
1
9
1
H), 6.34 (dd, J = 5.6, 1.7 Hz, 1H), 5.44 (dd, J = 3.5, 2.0 Hz, 2H); F NMR (282 MHz,
d -DMSO): δ -67.20 (s, 2F), -111.07 (d, J = 233.8 Hz, 1F), -123.19 (d, J = 233.8 Hz, 1F);
6
FF
FF
13
C NMR (100 MHz, CDCl ): δ 172.7, 153.8, 138.9, 127.4, 127.2, 126.5, 123.7, 85.7, 52.6;
3
+
MS (ESI) 400 [M+Na] ; Anal. Calcd for C H ClF NO S : C, 34.97; H, 2.13; N, 3.71; F,
11
8
4
3 2
26
2
0.12. Found C, 34.91; H, 2.17; N, 3.46; F, 20.23; [α] = -31.32 (c 1.10, CHCl3).
D
29