Diastereoselective Synthesis of CF3-Containing Vicinal Diamines

Article abstract of DOI:10.1021/acs.joc.7b01261

The highly diastereoselective synthesis of CF₃-containing vicinal diamines by a convenient two-step procedure without the need to isolate the intermediate products is described.

Full text of DOI:10.1021/acs.joc.7b01261

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Note
Diastereoselective synthesis of CF3-containing vicinal diamines
Qiu-Xia Huang, Qu-Tong Zheng, Yaya Duan, Jin-Hong Lin, Ji-Chang Xiao, and Xing Zheng
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.7b01261 • Publication Date (Web): 07 Jul 2017
Downloaded from http://pubs.acs.org on July 7, 2017
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Diastereoselective synthesis of CF3-containing
vicinal diamines
‡
‡
Qiuꢀxia Huang,a, b Quꢀtong Zheng,a, b Yaya Duan,b JinꢀHong Lin,b* JiꢀChang,
Xiaoa,b* and Xing Zhenga,b*
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aInstitute of Pharmacy and Pharmacology, Hunan Province Cooperative Innovation
Center for Molecular Target New Drug Study, University of South China, 28 Western
Changsheng Road, Hengyang, Hunan, 421001, China.
bKey Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic
Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences
345 Lingling Road, Shanghai 200032, China.
‡These two authors contributed equally to this work.
Abstract
The highly diastereoselective synthesis of CF3ꢀcontaining vicinal diamines by a
convenient twoꢀstep procedure without the need to isolate the intermediate products is
described.
Vicinal diamines represent highly important scaffolds in natural products,
pharmaceuticals, and agrochemicals.1 As trifluoromethyl group (CF3) have proved to
be a valuable pharmacophore in medicinal chemistry and agrochemistry,2 its
incorporation into vicinal diamines may improve biological properties. Indeed,
biologically active CF3ꢀcontaining vicinal diamines have appeared. For instance,
Flecainide is a commercially available drug which is used to prevent and treat
tachyarrhythmias (abnormal fast rhythms of the heart),3 and Sch 425078 has been
shown to be a potent neurokinin antagonist (Scheme 1)4. Therefore, it is highly
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desirable to develop mild protocols to access CF3ꢀvicinal diamines. Surprisingly,
although significant efforts have been directed towards the exploration of efficient
methods to prepare vicinal diamines,1e,5 the diastereoselective synthesis of
CF3ꢀcontaining vicinal diamines remains largely unexplored.
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Scheme 1. Biologically active CF3-containing vicinal diamines
Although CF3ꢀcontaining vicinal diamines could be easily obtained,6 their
diastereoselective synthesis has not been realized until recently. In 2014, D’hooghe,
De Kimpe et al. described the Lewis acidꢀpromoted ringꢀopening of aziridine to give
CF3ꢀvicinal diamines (Scheme 2, eq 1).7 Almost at the same time, Fustero and
coꢀworkers obtained the diamine derivatives by trifluoromethylation of αꢀamino
imines (eq 2).8 Although these examples represented a breakthrough in the
diastereoselective synthesis of CF3ꢀvicinal diamines, multiꢀstep procedure and low
yields limit their synthetic utility. In 2015, Han, Soloshonok et al. reported a twoꢀstep
procedure to achieve diamines in high yields (eq 3).9 Recently, the group of Waser
disclosed the Pdꢀcatalyzed threeꢀcomponent synthesis of diamines via in situ aminal
formation and carboamination (eq 4).10 In all of these reactions, high
diastereoselectivity was obtained (eqs. 1ꢀ4). But the convenient and diastereoselective
synthesis of CF3ꢀcontaining vicinal diamines remains a challenging task.
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Scheme 2. The synthesis of CF3-containing vicinal diamines
We have previously found that CF3ꢀaziridines could be easily prepared in high
yields and with high diastereoselectivity by cyclization of imines with sulfonium ylide
[Ph2S+CHꢀCF3] generated in situ from sulfonium salt 1 [Ph2S+CH2CF3 –OTf].11 We
speculated that ringꢀopening of CF3ꢀazirindes with amines may furnish
CF3ꢀcontaining vicinal diamines. In continuation of our research interest in the
incorporation of CF3 moiety,11ꢀ12 we have now investigated the convenient synthesis
of CF3ꢀvicinal diamines from imines without the need to isolate the intermediate
CF3ꢀaziridines (Scheme 2, eq 5).
The CF3ꢀaziridines we have made before were aryl aziridines.11 In this work, we
were interested in vinyl aziridines since the vinyl moiety is also a potential
functionality for further transformation. Therefore, we firstly tested if vinyl aziridines
could be easily obtained. To our delight, under the same conditions for cyclization of
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aryl imines,11 vinyl imines were converted smoothly into vinyl aziridines in high
yields (Scheme 3). High diastereoselectivity was observed in all reactions (cis:trans >
9:1). Although high yields were obtained for the conversion of electronꢀneutral and
ꢀrich imines, the desired products were unstable and therefore could not be isolated
(3a-3c). Interestingly, the presence of a bromoꢀsubstituent in the vinyl moiety could
stabilize the products (3d-3f). Electronꢀdeficient imines were well transformed and
the expected products were isolated in good yields (3g-3o). The structure and relative
configuration of product 3m were confirmed by single crystal Xꢀray diffraction.13
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Scheme 3. The synthesis of vinyl imines. Isolated yields. aThe yields in
parentheses were determined by 19F NMR spectrometry.
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Since the availability of CF3ꢀaziridines was not an issue, we then examined the
convenient synthesis of CF3ꢀvicinal diamines without isolating CF3ꢀaziridines. A
twoꢀstep procedure was performed, including cyclization of vinyl imine to give
aziridines (step 1) and ringꢀopening of aziridine by aryl amine (step 2) to afford the
desired product. To our delight, the oneꢀpot procedure by cyclization of substrate 2a
and the subsequent direct addition of 4ꢀmethylphenyl amine (4ꢀMeC6H4NH2) could
furnish product 4a in 56% yield (Table 1, entry 1). Elevating the reaction temperature
of step 2 increased the yield slightly (entry 2). DCM in step 2 should be replaced by
other solvent which has a higher boiling point, otherwise the reaction temperature
can’t be further elevated. 4 Å MS used in step 1 might have side effects on step 2
since it could act as a Lewis acid. Therefore, 4 Å MS was removed by filtration after
step 1. Indeed, the yield was further increased in DMA without 4 Å MS present in
step 2 (entry 3). A brief survey of the reaction solvent in step 2 (entries 3ꢀ7) revealed
that DMA was a suitable solvent (entry 3). Increasing the loading of amine led to the
decrease in the yield (entries 8ꢀ9). Slightly lower yields were obtained by lowering
(entries 10ꢀ11) or elevating (entry 12) the reaction temperature in step 2.
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Table 1. Screening conditions for the synthesis of CF3-vicinal diaminesa
entry
1d
2d
3
solvent
DCM
temp. (oC)
ratiob
yield (%)c
rt
reflux
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1 : 1 : 1.25:1
1 : 1 : 1.25:1
1 : 1 : 1.25:1
1 : 1 : 1.25:1
1 : 1 : 1.25:1
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65
DCM
DMA
NMP
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4
60
35
5
CH3CN
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trace
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THF
1,4ꢀDioxane
DMA
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60
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rt
1 : 1 : 1.25:1
1 : 1 : 1.25:1
1 : 1 : 1.25:1.25
1 : 1 : 1.25:1.7
1 : 1 : 1.25:1
1 : 1 : 1.25:1
1 : 1 : 1.25:1
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DMA
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DMA
DMA
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DMA
aReaction conditions: substrate 2a (0.2 mmol), salt 1, TBAF, 4Å MS (80 mg) in DCM (2 mL) at rt
under N2 atmosphere for 1 h (step 1). 4Å MS was removed by filtration. The filtrate was
concentrated to give crude aziridine, into which was added 4ꢀMeC6H4NH2 and solvent (2 mL)
under N2 atmosphere. The reaction system was further stirred at the indicated temperature for 2 h
b
c
(step 2); Molar ratio of 2a:1:TBAF:4ꢀMeC6H4NH2; The yields were determined by 19F NMR
d
spectrometry; After step 1, 4ꢀMeC6H4NH2 was added directly, and the resulting mixture was
further stirred to afford product 4a.
With the optimized reaction conditions in hand (Table 1, entry 3), we then
investigated the substrate scope of the convenient twoꢀstep reaction for the synthesis
of CF3ꢀvicinal diamines (Scheme 4). It is noteworthy that high diastereoselectivity
(syn:anti > 94:6) was observed for all reactions. Although electronꢀneutral and ꢀrich
aziridines (3a-3c in Scheme 3) were too unstable to be isolated, their corresponding
CF3ꢀvicinal diamines were isolated in moderate to good yields (Scheme 4, 4a-4g).
The structure and relative configuration of product 4b were confirmed by single
crystal Xꢀray diffraction.14 Moderate yields were obtained for the conversion of
electronꢀdeficient imines (4h-4l). Electronꢀrich (4a, 4d and 4j), ꢀneutral (4b, 4f, 4h
and 4k) and ꢀdeficient (4c, 4e, 4g, 4i and 4l) aryl amines were all effective to react
with aziridines to obtain diamines. Besides aryl amines, alkyl amine could also lead to
the ringꢀopening of aziridines to give CF3ꢀvicinal diamine (4m). In contrast to vinyl
imines, although aryl imine such as phenyl imine (PhCH=NHTs) could be converted
into aziridine, the resulting azirinde could not undergo further ringꢀopening with
amines to give vicinal diamines.
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Scheme 4. The synthesis of CF3ꢀvicinal diamines. Reaction conditions: substrate 2
(0.2 mmol), salt 1 (1 equiv), TBAF (0.25 mL, 1 M), 4Å MS (80 mg) in DCM (2 mL)
at rt for 1 h (step 1); 4Å MS was removed by filtration; The filtrate was concentrated
to give crude aziridine, into which was added amine (1 equiv) and DMA (2 mL); The
o
a
reaction system was further stirred at 60 C for 2 h (step 2). Isolated yields. The
yields in parentheses were determined by 19F NMR spectrometry.
Apparently, the twoꢀstep procedure is quite convenient for the preparation of
CF3ꢀcontaining vicinal diamines. Crude CF3ꢀaziridines were obtained simply by
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filtration and concentration, and the subsequent ringꢀopening reaction proceeded
smoothly to give diamines. Since purification of aziridines is avoided, this protocol is
attractive and promising.
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The synthesis of vicinal amino alcohols has also received a great deal of attention
due to the occurrence of vicinal amino alcohol motif in a vast range of natural
products, bioactive compounds, and reagents used for the stereoselective synthesis.15
The incorporation of CF3 moiety into vicinal amino alcohols may result in profound
modification of their physicochemical properties. Since CF3ꢀvicinal diamines could be
obtained by ringꢀopening of aziridines with amines, CF3ꢀcontaining vicinal amino
alcohols may also be prepared by ringꢀopening of aziridines with alkoxyl anion.
Indeed, the use of sodium methoxide and sodium phenylmethanolate as the
nucleophiles could give the desired product 5a and 5b, respectively, without the need
to isolating aziridines (Scheme 5). The structure and relative configuration of product
5a were confirmed by single crystal Xꢀray diffraction.16 The reduction of 5b
successfully gave the expected vicinal amino alcohol 6.
Scheme 5. The synthesis of CF3-containing vicinal amino alcohol derivative
In conclusion, we have described the efficient synthesis of CF3ꢀcontaining vicinal
diamines by a simple twoꢀstep procedure without the need to isolate the intermediate
products. The convenient procedure could also be applied to the preparation of
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CF3ꢀcontaining vicinal amino alcohol derivative. This work represents a mild protocol
for the incorporation of CF3 moiety into vicinal diamines with high
diastereoselectivity and in good yields. This twoꢀstep strategy may also find synthetic
utility in the incorporation of fluorinated group into other biologically active
compounds.
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EXPERIMENTAL SECTION
1
General Information. H, 13C and 19F NMR spectra were detected on a 500 MHz,
400 MHz or 300 MHz NMR spectrometer. Data for 1H NMR, 13C NMR and 19F NMR
were recorded as follows: chemical shift (δ, ppm), multiplicity (s = singlet, d =
doublet, t = triplet, m = multiplet, q = quartet, coupling constant (s) in Hz). Mass
spectra were obtained on GCꢀMS or LCꢀMS (ESI). High resolution mass data were
recorded on a high resolution mass spectrometer in the EI, ESI or MALDI mode. The
mass analyzer types for HRMSꢀEI, HRMSꢀESI, and HRMSꢀMALDI are time of flight,
Fourier transform mass spectrometer, and Fourier transform mass spectrometer,
respectively. Unless otherwise noted, all reagents were obtained commercially and
used without further purification. The 19F NMR yields were calculated based on the
19F NMR spectra of the reaction system with being added an internal standard
(PhCF3).
Procedure for the Synthesis of sulfonium salt 111: The mixture of
2,2,2ꢀtrifluoroethyl triflate (4.64 g, 20 mmol) and diphenyl sulfide (18.6 g, 100 mmol)
o
in a sealed tube was stirred at 150 C for 30 hours. After the reaction mixture was
cooled to room temperature, diethyl ether (10 mL) was added to precipitate the crude
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product, which was then washed with dry diethyl ether to give the final product 1 (5.9
g, 70% yield; 1H NMR (400 MHz, acetoneꢀd6) δ 8.36 (d, J = 7.6 Hz, 4H), 7.95 ꢀ 7.89
(m, 2H), 7.87 ꢀ 7.79 (m, 4H), 5.74 (q, J = 8.8 Hz, 2H). 19F NMR (376 MHz,
acetoneꢀd6) δ ꢀ61.26 (t, J = 8.8 Hz, 3F), ꢀ78.98 (s, 3F).
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General Procedure for the Synthesis of 2: Aldehyde (31.5 mmol), sulfonamide
(30 mmol) and tetraethyl orthosilicate (120 mmol) were mixed in a flask equipped
with a DeanꢀStark apparatus which was used to collect ethanol produced from the
reaction. The mixture was stirred at 160°C until no more ethanol was produced. After
the reaction system was cooled to room temperature, ethyl acetate/nꢀhexane (1:3) was
added to precipitate the crude product. After filtration, the solid was washed with
ethyl acetate/nꢀhexane(1:3) followed by ethanol to give the pure product 2.
(E)-4-Methyl-N-((E)-3-phenylallylidene)benzenesulfonamide (2a)17: 7.78 g, 91%
yield; 1H NMR (300 MHz, CDCl3) δ 8.78 (d, J = 9.4 Hz, 1H), 7.86 (d, J = 7.8 Hz, 2H),
7.60 ꢀ 7.39 (m, 6H), 7.34 (d, J = 7.8 Hz, 2H), 6.99 (dd, J = 15.7, 9.4 Hz, 1H), 2.44 (s,
3H).
(E)-4-Methyl-N-((E)-3-(p-tolyl)allylidene)benzenesulfonamide (2b)17: 8.52g, 95%
yield; 1H NMR (300 MHz, CDCl3) δ 8.76 (d, J = 9.4 Hz, 1H), 7.85 (d, J = 7.9 Hz, 2H),
7.50 ꢀ 7.41 (m, 3H), 7.33 (d, J = 7.9 Hz, 2H), 7.22 (d, J = 7.7 Hz, 2H), 6.94 (dd, J =
15.7, 9.4 Hz, 1H), 2.43 (s, 3H), 2.39 (s, 3H).
(E)-N-((E)-3-(3-Methoxyphenyl)allylidene)-4-methylbenzenesulfonamide (2c)18: 8.50
g, 90% yield; 1H NMR (400 MHz, CDCl3) δ 8.76 (d, J = 9.4 Hz, 1H), 7.86 (d, J = 8.0
Hz, 2H), 7.44 (d, J = 15.8 Hz, 1H), 7.35 ꢀ 7.28 (m, 3H), 7.13 (d, J = 7.5 Hz, 1H), 7.05
(s, 1H), 7.00 ꢀ 6.89 (m, 2H), 3.80 (s, 3H), 2.42 (s, 3H).
(E)-N-((Z)-2-Bromo-3-phenylallylidene)-4-methylbenzenesulfonamide (2d): Yellow
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solid, 6.10 g, 56% yield; M.P. 127.3 ꢀ 128.1 oC. 1H NMR (400 MHz, CDCl3) δ 8.74 (s,
1H), 7.98 (d, J = 5.8 Hz, 2H), 7.92 ꢀ 7.83 (m, 3H), 7.55 ꢀ 7.39 (m, 3H), 7.33 (d, J =
7.4 Hz, 2H), 2.43 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 169.5 (s), 151.2 (s), 144.8
(s), 134.9 (s), 133.3 (s), 131.8 (s), 131.2 (s), 129.9 (s), 128.7 (s), 128.1 (s), 118.5 (s),
21.7 (s). IR (neat) ν = 3050, 1611, 1583, 1570, 1449, 1330, 1300, 1289, 1147, 1084,
998, 864, 823, 811, 787, 755, 689, 669, 593, 573, 505 cmꢀ1. HRMS (MALDI/DHB):
calcd. for C16H15BrNO2S [M+H]+: 364.0001. Found: 364.0013.
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(Z)-N-((Z)-2-Bromo-3-(p-tolyl)allylidene)-4-methylbenzenesulfonamide (2e): Yellow
solid, 7.35 g, 65% yield; M.P. 145.3 ꢀ 147.1 oC. 1H NMR (500 MHz, CDCl3) δ 8.70 (s,
1H), 7.91 (d, J = 7.5 Hz, 2H), 7.89 (d, J = 7.5 Hz, 2H), 7.83 (s, 1H), 7.35 (d, J = 8.1
Hz, 2H), 7.28 (d, J = 8.1 Hz, 2H), 2.44 (s, 3H), 2.41 (s, 3H). 13C NMR (126 MHz,
CDCl3) δ 169.4 (s), 151.0 (s), 144.6 (s), 142.9 (s), 135.1 (s), 131.4 (s), 130.6 (s), 129.8
(s), 129.5 (s), 128.0 (s), 117.4 (s), 21.7 (s), 21.6 (s). IR (neat) ν = 3050, 2935, 2835,
1595, 1568, 1468, 1438, 1418, 1319, 1304, 1293, 1242, 1155, 1089, 1058, 1018, 823,
809, 698, 623, 587, 551 cmꢀ1. HRMS (ESI): calcd. for C17H17BrNO2S [M+H]+:
378.0158. Found: 378.0153.
(E)-N-((Z)-2-Bromo-3-(4-bromo-3-methoxyphenyl)allylidene)-4-methylbenzenesulf
1
onamide (2f): Yellow solid, 6.63 g, 47% yield; M.P. 145.3 ꢀ 147.1 oC. H NMR (500
MHz, CDCl3) δ 8.78 (s, 1H), 8.03 (s, 1H), 7.91 (d, J = 7.9 Hz, 2H), 7.65 (d, J = 2.1
Hz, 1H), 7.55 (d, J = 8.8 Hz, 1H), 7.38 (d, J = 7.9 Hz, 2H), 6.90 (dd, J = 8.8, 2.2 Hz,
1H), 3.83 (s, 3H), 2.46 (s, 3H). 13C NMR (126 MHz, CDCl3) δ 168.5 (s), 158.4 (s),
149.4 (s), 144.9 (s), 134.7 (s), 133.9 (s), 133.7 (s), 129.9 (s), 128.2 (s), 121.8 (s),
118.5 (s), 116.1 (s), 115.9 (s), 55.7 (s), 21.7 (s). IR (neat) ν = 3050, 2935, 2835, 1595,
1568, 1468, 1438, 1418, 1319, 1304, 1293, 1242, 1155, 1089, 1058, 1018, 823, 809,
698, 623, 587, 551 cmꢀ1. HRMS (ESI): calcd. for C17H16Br2NO3S [M+H]+: 471.9212.
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(E)-N-((E)-3-(4-Bromophenyl)allylidene)-4-methylbenzenesulfonamide (2g): Yellow
solid, 9.7 g, 89% yield; M.P. 191.7 ꢀ 192.3 oC. 1H NMR (400 MHz, CDCl3) δ 8.78 (d,
J = 9.3 Hz, 1H), 7.87 (d, J = 7.9 Hz, 2H), 7.57 (d, J = 8.1 Hz, 2H), 7.48 ꢀ 7.40 (m, 3H),
7.36 (d, J = 7.8 Hz, 2H), 6.97 (dd, J = 15.8, 9.4 Hz, 1H), 2.45 (s, 3H). 13C NMR (101
MHz, CDCl3) δ 170.5 (s), 152.0 (s), 144.6 (s), 135.2 (s), 133.0 (s), 132.5 (s), 129.8 (s),
129.8 (s), 128.0 (s), 126.1 (s), 125.3 (s), 21.6 (s). IR (neat) ν = 3020, 1621, 1591, 1574,
1486, 1404, 1316, 1304, 1289, 1156, 1085, 1070, 1002, 966, 859, 807, 777, 678, 590,
553 cmꢀ1. HRMS (ESI): calcd. for C16H14BrNNaO2S [M+Na]+: 385.9821. Found:
385.9809 .
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(E)-N-((E)-3-(2-Bromophenyl)allylidene)-4-methylbenzenesulfonamide (2h): Yellow
solid, 5.99 g, 55% yield; M.P. 123.4 ꢀ 124.9 oC. 1H NMR (400 MHz, CDCl3) δ 8.84 (d,
J = 9.4 Hz, 1H), 7.95 ꢀ 7.85 (m, 3H), 7.65 (d, J = 8.0 Hz, 1H), 7.64 (d, J = 8.0 Hz, 1H),
7.33 ꢀ 7.39 (m, 3H), 7.28 (td, J = 8.0, 1.6 Hz, 1H), 6.94 (dd, J = 15.8, 9.4 Hz, 1H),
2.45 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 170.5 (s), 151.4 (s), 144.6 (s), 135.1 (s),
133.9 (s), 133.7 (s), 132.4 (s), 129.8 (s), 128.0 (s), 128.0 (s), 128.0 (s), 126.9 (s),
125.9 (s), 21.6 (s). IR (neat) ν = 3029, 2360, 1915, 1618, 1578, 1440, 1372, 1314,
1303, 1287, 1168, 1153, 1088, 1009, 970, 855, 813, 774, 751, 683, 668, 581, 553 cmꢀ1.
HRMS (ESI): calcd. for C16H15BrNO2S [M+H]+: 364.0001. Found: 364.0001.
(E)-N-((E)-3-(4-Chlorophenyl)allylidene)-4-methylbenzenesulfonamide (2i)17: 8.13
g, 85% yield; 1H NMR (300 MHz, CDCl3) δ 8.76 (d, J = 9.3 Hz, 1H), 7.85 (d, J = 7.4
Hz, 2H), 7.60 ꢀ 7.27 (m, 7H), 6.94 (dd, J = 15.6, 9.3 Hz, 1H), 2.43 (s, 3H).
(E)-N-((E)-3-(4-Fluorophenyl)allylidene)-4-methylbenzenesulfonamide (2j): Yellow
solid, 6.45 g, 71% yield; M.P. 108.9 ꢀ 109.4 oC. 1H NMR (400 MHz, CDCl3) δ 8.77 (d,
J = 9.4 Hz, 1H), 7.85 (d, J = 8.3 Hz, 2H), 7.61 ꢀ 7.52 (m, 2H), 7.47 (d, J = 15.8 Hz,
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1H), 7.32 (d, J = 8.3 Hz, 2H), 7.09 (t, J = 8.3 Hz, 2H), 6.89 (dd, J = 15.8, 9.4 Hz, 1H),
2.41 (s, 3H). 19F NMR (376 MHz, CDCl3) δ ꢀ106.58 ꢀ ꢀ106.86 (m, 1F). 13C NMR (101
MHz, CDCl3) δ 170.8 (s), 164.5 (d, J = 254.0 Hz), 152.4 (s), 144.5 (s), 135.3 (s),
130.7 (d, J = 8.8 Hz), 130.5 (d, J = 3.3 Hz), 129.8 (s), 127.9 (s), 124.3 (s), 116.4 (d, J
= 22.1 Hz), 21.6 (s). IR (neat) ν = 3052, 1900, 1620, 1591, 1577, 1511, 1363, 1311,
1289, 1256, 1235, 1168, 1085, 1023, 976, 868, 823, 814, 800, 755, 681, 596, 552, 507
cmꢀ1. HRMS (ESI): calcd. for C16H15FNO2S [M+H]+: 304.0802. Found: 304.0807.
(E)-N-((E)-3-(3-Fluorophenyl)allylidene)-4-methylbenzenesulfonamide (2k): Yellow
solid, 4.54 g, 50% yield; M.P. 107.9 ꢀ 109.2 oC. 1H NMR (400 MHz, CDCl3) δ 8.75 (d,
J = 9.3 Hz, 1H), 7.83 (d, J = 8.3 Hz, 2H), 7.43 (d, J = 15.8 Hz, 1H), 7.40 ꢀ 7.27 (m,
4H), 7.20 (d, J = 9.5 Hz, 1H), 7.10 (td, J = 8.3, 1.6 Hz, 1H), 6.92 (dd, J = 15.8, 9.3 Hz,
1H), 2.41 (s, 3H). 19F NMR (376 MHz, CDCl3) δ ꢀ111.65 ꢀ ꢀ111.82 (m, 1F). 13C NMR
(101 MHz, CDCl3) δ 170.4 (s), 162.9 (d, J = 247.7 Hz), 151.9 (d, J = 2.8 Hz), 144.6
(s), 136.2 (d, J = 7.7 Hz), 135.0 (s), 130.7 (d, J = 8.3 Hz), 129.8 (s), 127.9 (s), 125.8
(s), 124.5 (d, J = 2.9 Hz), 118.3 (d, J = 21.4 Hz), 114.7 (d, J = 22.1 Hz), 21.6 (s). IR
(neat) ν = 3070, 1624, 1578, 1450, 1318, 1305, 1291, 1265, 1170, 1153, 1090, 963,
821, 803, 793, 786, 747, 680, 583, 550 cmꢀ1. HRMS (ESI): calcd. for C16H15FNO2S
[M+H]+: 304.0802. Found: 304.0801.
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(E)-N-((E)-3-(2-Fluorophenyl)allylidene)-4-methylbenzenesulfonamide (2l): Yellow
solid, 8.20 g, 90% yield; M.P. 99.3 ꢀ 99.9 oC. 1H NMR (400 MHz, CDCl3) δ 8.77 (d, J
= 9.4 Hz, 1H), 7.86 (d, J = 8.1 Hz, 2H), 7.62 (d, J = 16.0 Hz, 1H), 7.56 (t, J = 7.4 Hz,
1H), 7.47 ꢀ 7.37 (m, 1H), 7.34 (d, J = 8.1 Hz, 2H), 7.20 (t, J = 7.4 Hz, 1H), 7.12 (t, J =
7.4 Hz, 1H), 7.05 (dd, J = 16.0, 9.4 Hz, 1H), 2.43 (s, 3H). 19F NMR (376 MHz, CDCl3)
δ ꢀ113.57 ꢀ ꢀ113.75 (m, 1F). 13C NMR (101 MHz, CDCl3) δ 170.9 (s), 161.3 (d, J =
255.7 Hz), 145.8 (d, J = 3.2 Hz), 144.6 (s), 135.1 (s), 133.2 (d, J = 9.0 Hz), 129.8 (s),
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129.0 (s), 128.0 (s), 126.9 (d, J = 6.2 Hz), 124.8 (d, J = 3.6 Hz), 122.3 (d, J = 11.4 Hz),
116.4 (d, J = 21.7 Hz), 21.6 (s). IR (neat) ν = 3053, 2980, 1930, 1622, 1587, 1483,
1321, 1291, 1228, 1168, 1153, 1088, 1013, 973, 805, 770, 675, 588 cmꢀ1. HRMS
(MALDI/DHB): calcd. for C16H15FNO2S [M+H]+: 304.0802. Found: 304.0812.
(E)-4-Methyl-N-((E)-3-(4-nitrophenyl)allylidene)benzenesulfonamide (2m)18: 9.01 g,
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91% yield; H NMR (300 MHz, CDCl3) δ 8.80 (d, J = 9.1 Hz, 1H), 8.28 (d, J = 7.1
Hz, 2H), 7.86 (d, J = 6.9 Hz, 2H), 7.70 (d, J = 6.9 Hz, 2H), 7.52 (d, J = 15.8 Hz, 1H),
7.36 (d, J = 7.1 Hz, 2H), 7.08 (dd, J = 15.8, 9.1 Hz, 1H), 2.45 (s, 3H).
(E)-N-((E)-3-(4-Cyanophenyl)allylidene)-4-methylbenzenesulfonamide (2n): Yellow
solid, 4.74 g, 51% yield; M.P. 188.9 ꢀ 190.2 oC. 1H NMR (400 MHz, CDC3) δ 8.78 (d,
J = 9.2 Hz, 1H), 7.85 (d, J = 8.1 Hz, 2H), 7.70 (d, J = 8.3 Hz, 2H), 7.63 (d, J = 8.3 Hz,
2H), 7.47 (d, J = 15.9 Hz, 1H), 7.35 (d, J = 8.1 Hz, 2H), 7.04 (dd, J = 15.9, 9.2 Hz,
1H), 2.44 (s, 3H). 13C NMR (126 MHz, CDCl3) δ 169.6 (s), 150.0 (s), 144.8 (s), 138.1
(s), 134.8 (s), 132.8 (s), 129.9 (s), 128.7 (s), 128.1 (s), 127.8 (s), 118.0 (s), 114.4 (s),
21.6 (s). IR (neat) ν = 3051, 2224, 1626, 1607, 1582, 1414, 1314, 1289, 1260, 1180,
1156, 1089, 1017, 997, 964, 875, 820, 805, 782, 683, 597, 558, 545 cmꢀ1. HRMS
(ESI): calcd. for C17H15N2O2S [M+H]+: 311.0849. Found: 311.0847.
(E)-4-Methyl-N-((E)-3-(3-(trifluoromethyl) phenyl) allylidene) benzenesulfonamide
1
(2o): Yellow solid, 5.51 g, 52% yield; M.P. 107.4 ꢀ 108.7 oC. H NMR (400 MHz,
CDCl3) δ 8.81 (d, J = 9.3 Hz, 1H), 7.88 (d, J = 8.2 Hz, 2H), 7.79 (s, 1H), 7.75 (d, J =
7.8 Hz, 1H), 7.71 (d, J = 7.8 Hz, 1H), 7.59 (t, J = 7.8 Hz, 1H), 7.52 (d, J = 15.9 Hz,
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1H), 7.37 (d, J = 8.2 Hz, 2H), 7.06 (dd, J = 15.9, 9.3 Hz, 1H), 2.47 (s, 3H). F NMR
(376 MHz, CDCl3) δ ꢀ61.40 ꢀ ꢀ65.31 (m, 3F). 13C NMR (101 MHz, CDCl3) δ 170.0
(s), 151.0 (s), 144.7 (s), 135.0 (s), 134.9 (s), 131.8 (q, J = 32.8 Hz), 131.2 (s), 129.8
(s), 129.8 (s), 128.0 (s), 127.7 (q, J = 3.6 Hz), 126.5 (s), 125.1 (q, J = 3.8 Hz), 123.5
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(q, J = 272.6 Hz), 21.6 (s). IR (neat) ν = 3029, 1626, 1595, 1581, 1566, 1334, 1314,
1291, 1250, 1206, 1170, 1131, 1092, 1072, 1011, 969, 803, 790, 755, 694, 679, 665,
589, 553 cmꢀ1. HRMS (ESI): calcd. for C17H15F3NO2S [M+H]+: 354.0770. Found:
354.0768.
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Procedure
for
the
Synthesis
of
3:
Into
the
mixture
of
diphenyl(2,2,2ꢀTrifluoroethyl)sulfonium triflate 1 ( 209.2 mg, 0.5 mmol ), imine 2 (1
mmol) and 4Å MS (400 mg) in dichloromethane (10 mL) was added TBAF (0.75 mL,
1 M in THF) dropwise under N2 atmosphere. The reaction mixture was stirred at room
temperature for 1 h. After filtration, the solid was washed with DCM (10 mL). The
combined organic phase was washed with water, sat. sodium bisulfite and water in
sequence and then dried over Na2SO4. The solvent was removed by concentration,
and the residue was subjected to flash column chromatography with hexane/ethyl
acetate (50:1ꢀ20:1) as the eluent to afford the final product 3.
(2SR,3RS)-2-((Z)-1-Bromo-2-phenylvinyl)-1-tosyl-3-(trifluoromethyl)aziridine (3d):
Yellow solid, 204.7 mg, 92% yield; M.P. 118.0 ꢀ 118.8 oC. 1H NMR (500 MHz, CDCl3)
δ 7.94 (d, J = 8.2 Hz, 2H), 7.53 (d, J = 6.9 Hz, 2H), 7.43 (d, J = 8.2 Hz, 2H), 7.41 ꢀ
7.31 (m, 3H), 7.11 (s, 1H), 3.96 (d, J = 6.8 Hz, 1H), 3.52 ꢀ 3.42 (m, 1H), 2.50 (s, 3H).
19F NMR (376 MHz, CDCl3) δ ꢀ65.86 (d, J = 5.2 Hz, 3F). 13C NMR (126 MHz,
CDCl3) δ 146.0 (s), 134.0 (s), 133.0 (s), 131.4 (q, J = 1.2 Hz), 130.1 (s), 128.9 (s),
128.7 (s), 128.3 (s), 128.2 (s), 122.0 (q, J = 276.0 Hz), 111.5 (s), 46.4 (q, J = 1.2 Hz),
42.7 (q, J = 40.5 Hz), 21.7 (s). IR (neat) ν = 3068, 3022, 2975, 2926, 1595, 1493,
1447, 1428, 1365, 1338, 1283, 1198, 1186, 1163, 1104, 1088, 1021, 935, 923, 862,
813, 771, 756, 692, 675, 548, 525 cmꢀ1. HRMS (ESI): calcd. for C18H15BrF3NNaO2S
[M+Na]+: 467.9851. Found: 467.9849.
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(2SR,3RS)-2-((Z)-1-Bromo-2-(p-tolyl)vinyl)-1-tosyl-3-(trifluoromethyl)aziridine
(3e): Yellow solid, 183.6 mg, 80% yield; M.P. 124.45 ꢀ 125.56 oC. 1H NMR (400 MHz,
CDCl3) δ 7.94 (d, J = 8.1 Hz, 2H), 7.46 ꢀ 7.44 (m, 4H), 7.18 (d, J = 8.1 Hz, 2H), 7.07
(s, 1H), 3.95 (d, J = 6.7 Hz, 1H), 3.51 ꢀ 3.38 (m, 1H), 2.51 (s, 3H), 2.37 (s, 3H). 19F
NMR (376 MHz, CDCl3) δ ꢀ65.90 (d, J = 5.2 Hz, 3F). 13C NMR (101 MHz, CDCl3) δ
146.0 (s), 138.8 (s), 133.1 (s), 131.3 (s), 131.2 (s), 130.1 (s), 128.9 (s), 128.9 (s),
128.3 (s), 122.0 (q, J = 276.0 Hz), 110.5 (s), 46.4 (s), 42.7 (q, J = 40.4 Hz), 21.7 (s),
21.3 (s). IR (neat) ν = 3030, 2978, 2922, 1609, 1597, 1512, 1438, 1364, 1342, 1284,
1181, 1166, 1150, 1090, 1021, 934, 910, 882, 869, 812, 801, 792, 751, 674, 610, 547,
527 cmꢀ1. HRMS (ESI): calcd. for C19H17BrF3NNaO2S [M+Na]+: 482.0008. Found:
482.0011.
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methyl)aziridine (3f): Yellow solid, 248.4 mg, 90% yield; M.P. 97.3 ꢀ 98.5 oC. H
NMR (400 MHz, CDCl3) δ 7.92 (d, J = 8.3 Hz, 2H), 7.44 ꢀ 7.37 (m, 3H), 7.10 (d, J =
3.0 Hz, 1H), 7.06 (s, 1H), 6.73 (dd, J = 8.8, 3.0 Hz, 1H), 3.90 (d, J = 6.8 Hz, 1H),
3.77 (s, 3H), 3.56 ꢀ 3.48 (m, 1H), 2.47 (s, 3H). 19F NMR (376 MHz, CDCl3) δ ꢀ65.80
(d, J = 5.1 Hz, 3F).13C NMR (126 MHz, CDCl3) δ 158.3 (s), 146.0 (s), 135.3 (s),
133.1 (s), 133.0 (s), 131.4 (s), 130.2 (s), 128.3 (s), 121.9 (q, J = 272.3 Hz), 115.9 (s),
115.8 (s), 114.6 (s), 114.0 (s), 55.5 (s), 46.5 (s), 42.1 (q, J = 40.7 Hz), 21.7 (s). IR
(neat) ν = 3022, 2966, 2941, 2835, 1592, 1468, 1444, 1403, 1372, 1338, 1317, 1295,
1238, 1213, 1167, 1145, 1088, 1049, 1022, 905, 931, 865, 818, 793, 745, 678, 609,
558, 532 cmꢀ1. HRMS (ESI): calcd. for C19H16Br2F3NNaO3S [M+Na]+: 575.9062.
Found: 575.9034.
(2R,3R)-2-((E)-4-Bromostyryl)-1-tosyl-3-(trifluoromethyl)aziridine (3g): Yellow
solid, 189.1 mg, 85% yield; M.P. 72.7 ꢀ 73.7 oC. 1H NMR (400 MHz, CDCl3) δ 7.86
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(d, J = 8.3 Hz, 2H), 7.43 (d, J = 8.4 Hz, 2H), 7.37 (d, J = 8.3 Hz, 2H), 7.20 (d, J = 8.4
Hz, 2H), 6.81 (d, J = 16.0 Hz, 1H), 5.98 (ddd, J = 16.0, 8.4, 1.2 Hz, 1H), 3.75 (t, J =
7
8
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7.7 Hz, 1H), 3.49 ꢀ 3.36 (m, 1H), 2.44 (s, 3H). F NMR (376 MHz, CDCl3) δ ꢀ66.01
9
(d, J = 5.7 Hz, 3F). 13C NMR (126 MHz, CDCl3) δ 145.6 (s), 137.3 (s), 134.2 (s),
133.6 (s), 131.8 (s), 130.0 (s), 128.2 (s), 128.0 (s), 122.7 (s), 122.4 (q, J = 275.5 Hz),
119.4 (s), 43.8 (q, J = 0.7 Hz), 42.3 (q, J = 40.1 Hz), 21.7 (s). IR (neat) ν = 3041, 2956,
1742, 1684, 1653, 1596, 1488, 1440, 1407, 1336, 1305, 1291, 1233, 1164, 1110, 1070,
1017, 1008, 938, 857, 828, 840, 755, 670, 600, 553 cmꢀ1. HRMS (ESI): calcd. for
C18H15BrF3NNaO2S [M+Na]+: 467.9851. Found: 467.9845.
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(2RS,3RS)-2-((E)-2-Bromostyryl)-1-tosyl-3-(trifluoromethyl)aziridine (3h): Yellow
solid, 185 mg, 83% yield; M.P. 85.9 ꢀ 86.3 oC. 1H NMR (400 MHz, CDCl3) δ 7.85 (d,
J = 8.0 Hz, 2H), 7.53 (d, J = 7.9 Hz, 1H), 7.42 (d, J = 7.5 Hz, 1H), 7.36 (d, J = 8.0 Hz,
2H), 7.25 ꢀ 7.17 (m, 2H), 7.12 (t, J = 7.5 Hz, 1H), 5.92 (dd, J = 15.6, 8.3 Hz, 1H),
3.78 (t, J = 7.5 Hz, 1H), 3.51 ꢀ 3.39 (m, 1H), 2.44 (s, 3H). 19F NMR (376 MHz, CDCl3)
δ ꢀ65.98 (d, J = 5.9 Hz, 3F).13C NMR (101 MHz, CDCl3) δ 145.6 (s), 137.1 (s), 135.1
(s), 133.5 (s), 133.0 (s), 130.0 (s), 129.9 (s), 128.0 (s), 127.5 (s), 127.1 (s), 123.7 (s),
122.4 (q, J = 275.8 Hz), 121.4 (s), 43.9 (s), 42.0 (q, J = 40.2 Hz), 21.7 (s). IR (neat) ν
= 3062, 3009, 2927, 1598, 1469, 1432, 1389, 1338, 1296, 1277, 1203, 1158, 1089,
1026, 971, 947, 852, 830, 815, 757, 748, 678, 599, 569, 557, 540 cmꢀ1. HRMS (ESI):
calcd. for C18H16BrF3NO2S [M+H]+: 446.0032. Found: 446.0028.
(2RS,3RS)-2-((E)-4-Chlorostyryl)-1-tosyl-3-(trifluoromethyl)aziridine
(3i):
1
Yellow solid, 156.4 mg, 78% yield; M.P. 77.3 ꢀ 78.9 oC. H NMR (500 MHz, CDCl3)
δ 7.87 (d, J = 8.2 Hz, 2H), 7.39 (d, J = 8.2 Hz, 2H), 7.33 ꢀ 7.26 (m, 4H), 6.84 (d, J =
15.9 Hz, 1H), 5.98 (dd, J = 15.9, 8.5 Hz, 1H), 3.76 (t, J = 7.7 Hz, 1H), 3.49 ꢀ 3.37 (m,
1H), 2.47 (s, 3H). 19F NMR (376 MHz, CDCl3) δ ꢀ66.04 (d, J = 5.6 Hz, 3F).13C NMR
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(126 MHz, CDCl3) δ 145.6 (s), 137.2 (s), 134.5 (s), 133.8 (s), 133.7 (s), 130.0 (s),
128.9 (s), 128.0 (s), 127.9 (s), 122.4 (q, J = 275.2 Hz), 119.2 (s), 43.8 (s), 42.3 (q, J =
40.1 Hz), 21.7 (s). IR (neat) ν = 3029, 2964, 1652, 1597, 1507, 1491, 1435, 1409,
1336, 1286, 1277, 1229, 1188, 1162,1148, 1088, 1024, 1011, 973, 867, 842, 809, 749,
682, 670, 566, 471 cmꢀ1. HRMS (ESI): calcd. for C18H15ClF3NNaO2S [M+Na]+:
424.0356. Found: 424.0361. Elemental Analysis: calcd. for C18H15ClF3NO2S C, 53.80;
H, 3.76; N, 3.49. Found: C, 53.67; H, 3.94; N, 3.50.
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(2RS,3RS)-2-((E)-4-Fluorostyryl)-1-tosyl-3-(trifluoromethyl)aziridine (3j): Yellow
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solid, 115.5 mg, 60% yield; M.P. 74.1 ꢀ 75.6 oC. H NMR (500 MHz, CDCl3) δ 7.87
(d, J = 8.0 Hz, 2H), 7.39 (d, J = 8.0 Hz, 2H), 7.36 ꢀ 7.32 (m, 2H), 7.02 (t, J = 8.2 Hz,
2H), 6.85 (d, J = 15.8 Hz, 1H), 5.92 (dd, J = 15.8, 8.5 Hz, 1H), 3.77 (t, J = 7.7 Hz,
1H), 3.48 ꢀ 3.37 (m, 1H), 2.47 (s, 3H). 19F NMR (376 MHz, CDCl3) δ ꢀ66.03 (d, J =
5.7 Hz, 3F), ꢀ112.27 ꢀ ꢀ112.37 (m, 1F). 13C NMR (126 MHz, CDCl3) δ 162.9 (d, J =
248.7 Hz), 145.5 (s), 137.3 (s), 133.7 (s), 131.5 (d, J = 3.3 Hz), 129.9 (s), 128.4 (d, J
= 8.4 Hz), 128.0 (s), 122.5 (q, J = 275.4 Hz), 118.3 (s), 115.6 (d, J = 21.8 Hz), 43.9 (s),
42.2 (q, J = 40.1 Hz), 21.7 (s). IR (neat) ν = 3038, 2926, 1654, 1600, 1508, 1431,
1417, 1342, 1278, 1222, 1187, 1162, 1089, 1028, 970, 947, 857, 816, 747, 675, 599,
572, 545 cmꢀ1. HRMS (ESI): calcd. for C18H15F4NNaO2S [M+Na]+: 408.0652.
Found:408.0653.
(2RS,3RS)-2-((E)-3-Fluorostyryl)-1-tosyl-3-(trifluoromethyl)aziridine (3k): Yellow
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liquid, 145 mg, 75% yield; H NMR (400 MHz, CDCl3) δ 7.86 (d, J = 8.2 Hz, 2H),
7.37 (d, J = 8.2 Hz, 2H), 7.33 ꢀ 7.24 (m, 1H), 7.11 (d, J = 7.7 Hz, 1H), 7.06 ꢀ 7.02 (m,
1H), 6.97 (td, J = 8.3, 1.8 Hz, 1H), 6.83 (d, J = 15.9 Hz, 1H), 6.00 (ddd, J = 15.9, 8.3,
1.4 Hz, 1H), 3.76 (t, J = 7.7 Hz, 1H), 3.52 ꢀ 3.37 (m, 1H), 2.45 (s, 3H). 19F NMR (376
MHz, CDCl3) δ ꢀ66.04 (d, J = 5.9 Hz, 3F), ꢀ112.98 (td, J = 9.1, 6.1 Hz, 1F).13C NMR
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(126 MHz, CDCl3) δ 162.9 (d, J = 246.1 Hz), 145.6 (s), 137.5 (d, J = 7.7 Hz), 137.2
(s), 133.6 (s), 130.2 (d, J = 8.3 Hz), 130.0 (s), 128.1 (s), 122.6 (d, J = 2.8 Hz), 122.4
(q, J = 275.3 Hz), 120.1 (s), 115.58 (d, J = 21.4 Hz), 113.1 (d, J = 22.0 Hz), 43.6 (s),
42.28 (q, J = 40.2 Hz), 21.7 (s). IR (neat) ν = 3035, 2924, 1611, 1598, 1585, 1490,
1448, 1340, 1293, 1274, 1214, 1166, 1091, 1025, 972, 928, 872, 849, 818, 758, 746,
678, 585 cmꢀ1. HRMS (ESI): calcd. for C18H16F4NO2S [M+H]+: 386.0832. Found:
386.0830.
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(2RS,3RS)-2-((E)-2-Fluorostyryl)-1-tosyl-3-(trifluoromethyl)aziridine (3l): Yellow
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solid, 129.5 mg, 67% yield; M.P. 76.6 ꢀ 78.3 oC. H NMR (400 MHz, CDCl3) δ 7.86
(d, J = 8.3 Hz, 2H), 7.41 ꢀ 7.33 (m, 3H), 7.30 ꢀ 7.20 (m, 1H), 7.10 ꢀ 6.97 (m, 3H), 6.09
(ddd, J = 16.1, 8.5, 1.5 Hz, 1H), 3.76 (t, J = 7.7 Hz, 1H), 3.54 ꢀ 3.31 (m, 1H), 2.43 (s,
3H). 19F NMR (376 MHz, CDCl3) δ ꢀ66.00 (d, J = 5.7 Hz, 3F), ꢀ117.12 (ddd, J = 10.9,
7.5, 5.3 Hz, 1F).13C NMR (101 MHz, CDCl3) δ 160.3 (d, J = 251.0 Hz), 145.6 (s),
133.7 (s), 131.0 (d, J = 3.2 Hz), 130.1 (d, J = 8.5 Hz), 130.0 (s), 128.1 (s), 127.7 (d, J
= 3.3 Hz), 124.2 (d, J = 3.6 Hz), 123.2 (d, J = 11.9 Hz), 122.5 (q, J = 274.4 Hz), 121.2
(s), 115.8 (d, J = 21.9 Hz), 44.2 (s), 42.2 (q, J = 40.2 Hz), 21.6 (s). IR (neat) ν = 3068,
3021, 2926, 1612, 1598, 1581, 1491, 1457, 1436, 1391, 1339, 1306, 1288, 1260, 1235,
1224, 1190, 1152, 1091, 1023, 974, 943, 874, 853, 844, 823, 764, 678, 558, 525 cmꢀ1.
HRMS (ESI): calcd. for C18H16F4NO2S [M+H]+: 386.0832. Found: 386.0830.
(2RS,3RS)-2-((E)-4-Nitrostyryl)-1-tosyl-3-(trifluoromethyl)aziridine (3m): Yellow
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solid, 179.5 mg, 86% yield; M.P. 74.5 ꢀ 75.6 oC. H NMR (400 MHz, CDCl3) δ 8.21
(d, J = 8.8 Hz, 2H), 7.89 (d, J = 8.2 Hz, 2H), 7.52 (d, J = 8.8 Hz, 2H), 7.41 (d, J = 8.2
Hz, 2H), 6.97 (d, J = 16.0 Hz, 1H), 6.19 (dd, J = 16.0, 8.2 Hz, 1H), 3.81 (t, J = 7.7 Hz,
1H), 3.55 ꢀ 3.39 (m, 1H), 2.49 (s, 3H). 19F NMR (376 MHz, CDCl3) δ ꢀ66.00 (d, J =
5.8 Hz, 3F). 13C NMR (101 MHz, CDCl3) δ 147.6 (s), 145.8 (s), 141.4 (s), 136.1 (s),
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133.5 (s), 130.0 (s), 128.1 (s), 127.3 (s), 124.1 (s), 123.5 (s), 122.3 (q, J = 275.3 Hz),
43.0 (s), 42.5 (q, J = 38.7 Hz), 21.7 (s). IR (neat) ν = 3039, 2931, 1596, 1517, 1495,
1441, 1417, 1347, 1304, 1283, 1229, 1206, 1187, 1163, 1107, 1091, 1016, 938, 867,
839, 822, 808, 759, 744, 672, 600 cmꢀ1. HRMS (MALDI/DHB): calcd. for
C18H16F3N2O4S [M+H]+: 413.0777. Found: 413.0788.
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4-((E)-2-((2RS,3RS)-1-Tosyl-3-(trifluoromethyl)aziridin-2-yl)vinyl)benzonitrile (3n):
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Yellow solid, 174.2 mg, 89% yield; M.P. 71.2 ꢀ 72.0 oC. H NMR (400 MHz, CDCl3)
δ 7.85 (d, J = 7.9 Hz, 2H), 7.60 (d, J = 7.7 Hz, 2H), 7.43 (d, J = 7.9 Hz, 2H), 7.38 (d,
J = 7.7 Hz, 2H), 6.89 (d, J = 15.9 Hz, 1H), 6.11 (dd, J = 15.9, 8.1 Hz, 1H), 3.77 (t, J =
7.7 Hz, 1H), 3.50 ꢀ 3.33 (m, 1H), 2.46 (s, 3H). 19F NMR (376 MHz, CDCl3) δ ꢀ66.58
(d, J = 5.8 Hz, 3F). 13C NMR (101 MHz, CDCl3) δ 145.8 (s), 139.6 (s), 136.5 (s),
133.5 (s), 132.5 (s), 130.0 (s), 128.1 (s), 127.2 (s), 122.7 (s), 122.3 (q, J = 276.0 Hz),
118.5 (s), 112.0 (s), 43.2 (s), 42.4 (q, J = 39.8 Hz), 21.7 (s). IR (neat) ν = 3024, 2964,
2227, 1607, 1600, 1437, 1412, 1391, 1376, 1330, 1308, 1293, 1281, 1207, 1164, 1140,
1103, 1092, 1032, 967, 948, 856, 829, 818, 750, 676, 601, 571, 556 cmꢀ1. HRMS
(ESI): calcd. for C19H16F3N2O2S [M+H]+: 393.0879. Found: 393.0878.
(2RS,3RS)-1-Tosyl-2-(trifluoromethyl)-3-((E)-3-(trifluoromethyl)styryl)aziridine
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(3o): Yellow solid, 177.3 mg, 82% yield; M.P. 85.3 ꢀ 87.0 oC. H NMR (400 MHz,
CDCl3) δ 7.86 (d, J = 8.3 Hz, 2H), 7.57 (s, 1H), 7.55 ꢀ 7.50 (m, 2H), 7.48 ꢀ 7.41 (m,
1H), 7.38 (d, J = 8.3 Hz, 2H), 6.90 (d, J = 16.0 Hz, 1H), 6.06 (ddd, J = 16.0, 8.2, 1.2
Hz, 1H), 3.77 (t, J = 7.6 Hz, 1H), 3.48 ꢀ 3.40 (m, 1H), 2.46 (s, 3H). 19F NMR (376
MHz, CDCl3) δ ꢀ62.90 (s, 3F), ꢀ66.05 (d, J = 5.8 Hz, 3F). 13C NMR (126 MHz,
CDCl3) δ 145.7 (s), 136.9 (s), 136.0 (s), 133.6 (s), 131.2 (q, J = 32.4 Hz), 130.0 (s),
129.7 (q, J = 1.2 Hz), 129.2 (s), 128.1 (s), 125.2 (q, J = 3.8 Hz), 124.2 (q, J = 274.1
Hz), 123.4 (q, J = 3.8 Hz), 122.4 (q, J = 275.4 Hz), 120.7 (s), 43.5 (s), 42.3 (q, J =
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40.2 Hz), 21.7 (s). IR (neat) ν = 3074, 3023, 2930, 1599, 1493, 1451, 1430, 1392,
1332, 1282, 1234, 1201, 1158, 1126, 1090, 1070, 1033, 984, 950, 887, 844, 821, 799,
746, 680, 599, 556 cmꢀ1. HRMS (ESI): calcd. for C19H15F6NNaO2S [M+Na]+:
458.0620. Found: 458.0611.
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Procedure
for
the
Synthesis
of
4:
Into
a
mixture
of
diphenyl(2,2,2ꢀtrifluoroethyl)sulfonium triflate 1 (0.2 mmol), imine 2 (0.2 mmol) and
4Å MS (80 mg) in dichloromethane (2 mL) was added TBAF (0.25 mL, 1 M in THF)
dropwise under N2 atmosphere. The reaction mixture was stirred at room temperature
for 1 h. 4Å MS was removed by filtration. The filtrate was concentrated to give crude
aziridine, into which was added aryl amine (0.2 mmol) and DMA (2 mL) under N2
atmosphere. The reaction mixture was stirred at 60 oC for 2 h. After being cooled to
room temperature, the solution was subjected to flash column chromatography
(petroleum ether:EA = 20:1) to afford the pure product.
4-Methyl-N-((2S,E)-1,1,1-trifluoro-5-phenyl-3-(p-tolylamino)pent-4-en-2-yl)benzen
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esulfonamidenamide (4a): Yellow liquid, 66.3 mg, 70% yield ; H NMR (400 MHz,
CDCl3) δ 7.74 (d, J = 8.2 Hz, 2H), 7.35 ꢀ 7.17 (m, 7H), 6.98 (d, J = 8.1 Hz, 2H), 6.67
ꢀ 6.50 (m, 3H), 6.03 (dd, J = 15.8, 7.4 Hz, 1H), 5.38 (d, J = 9.5 Hz, 1H), 4.41 ꢀ 4.28
(m, 1H), 4.22 ꢀ 4.04 (m, 1H), 3.68 (br, 1H), 2.38 (s, 3H), 2.22 (s, 3H). 19F NMR (376
13
MHz, CDCl3) δ ꢀ71.00 (d, J = 7.2 Hz, 3F). C NMR (101 MHz, CDCl3) δ 144.1 (s),
143.4 (s), 137.1 (s), 135.9 (s), 133.5 (s), 129.9 (s), 129.8 (s), 128.5 (s), 128.3 (s),
128.1 (s), 127.1 (s), 126.7 (s), 125.3 (s), 124.4 (q, J = 283.9 Hz), 114.4 (s), 57.6 (q, J
= 28.1 Hz), 56.3 (s), 21.5 (s), 20.4 (s). IR (neat) ν =549.6, 568.9, 667.6, 694.2, 750.3,
811.5, 966.7, 1092.3, 1160.3, 1265.3, 1329.8, 1448.8, 1520.6, 1598.1, 1616.8, 2921.2,
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3027.2, 3282.4 cmꢀ1. HRMS (ESI): calcd. for C25H25O2N2F3NaS [M+Na]+: 497.1481.
Found: 497.1479.
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esulfonamide (4b): Yellow solid, 45.8 mg, 50% yield; M.P. 151 ꢀ 153oC. 1H NMR
(400 MHz, CDCl3) δ 7.76 (d, J = 8.2 Hz, 2H), 7.32 ꢀ 7.23 (m, 5H), 7.23 ꢀ 7.14 (m,
4H), 6.77 (t, J = 7.3 Hz, 1H), 6.67 ꢀ 6.56 (m, 3H), 6.05 (dd, J = 15.7, 7.0 Hz, 1H),
5.74 (d, J = 6.6 Hz, 1H), 4.50 ꢀ 4.39 (m, 1H), 4.22 ꢀ 4.11 (m, 1H), 3.93 (d, J = 8.6 Hz,
1H), 2.36 (s, 3H). 19F NMR (376 MHz, CDCl3) δ ꢀ70.92 (d, J = 7.3 Hz, 3F). 13C NMR
(101 MHz, CDCl3) δ 145.7 (s), 144.2 (s), 137.0 (s), 135.8 (s), 133.7 (s), 129.8 (s),
129.4 (s), 128.6 (s), 128.2 (s), 127.1 (s), 126.7 (s), 125.0 (s), 124.3 (q, J = 281.5 Hz),
119.0 (s), 114.1 (s), 57.5 (q, J = 28.2 Hz), 56.0 (s), 21.5 (s). IR (neat) ν = 547.6, 570.6,
688.8, 704.2, 765.1, 812.2, 959.9, 970.8, 1091.8, 1155.5, 1187.5, 1266.7, 1327.3,
1349.1, 1448.1, 1497.6, 1602.2, 2924.6, 324.91, 3363.5, 3413.8 cmꢀ1. HRMS (ESI):
calcd. for C24H22O2N2F3S [MꢀH]ꢀ: 459.1354. Found: 459.1356.
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-methylbenzenesulfonamide (4c): Yellow solid, 64.3 mg, 65% yield; M.P. 120 ꢀ 122
oC. 1H NMR (400 MHz, CDCl3) δ 7.73 (d, J = 8.2 Hz, 2H), 7.35 ꢀ 7.18 (m, 7H), 7.10
(d, J = 8.8 Hz, 2H), 6.66 ꢀ 6.49 (m, 3H), 6.02 (dd, J = 15.9, 7.0 Hz, 1H), 5.53 (d, J =
9.8 Hz, 1H), 4.40 ꢀ 4.32 (m, 1H), 4.19 ꢀ 4.07 (m, 1H), 3.94 (s, 1H), 2.37 (s, 3H). 19F
NMR (376 MHz, CDCl3) δ ꢀ71.01 (d, J = 7.3 Hz, 3F). 13C NMR (101 MHz, CDCl3) δ
144.4 (s), 144.3 (s), 136.9 (s), 135.6 (s), 133.7 (s), 129.8 (s), 129.2 (s), 128.6 (s),
128.2 (s), 127.0 (s), 126.7 (s), 124.8 (s), 124.2 (q, J = 283.8 Hz), 123.4 (s), 115.2 (s),
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57.6 (q, J = 28.9 Hz), 55.9 (s), 21.5 (s). IR (neat) ν = 502.81, 549.39, 568.84, 666.12,
692.63, 732.87, 752.07, 814.30, 909.86, 967.02, 1004.82, 1091.91, 1159.77, 1185.36,
1266.44, 1328.80, 1403.43, 1448.87, 1493.68, 1598.89, 2923.74, 3028.61, 3275.04
cmꢀ1. HRMS (ESI): calcd. for C24H23O2N2ClF3S [M+H]+: 495.1115. Found:
495.1115.
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nesulfonamide (4d): Yellow liquid, 49.7 mg, 51% yield; 1H NMR (400 MHz, CDCl3)
δ 7.75 (d, J = 8.2 Hz, 2H), 7.23 (d, J = 8.4 Hz, 2H), 7.17 (d, J = 8.0 Hz, 2H), 7.09 (d,
J = 7.9 Hz, 2H), 6.98 (d, J = 8.1 Hz, 2H), 6.61 ꢀ 6.48 (m, 3H), 5.97 (dd, J = 15.6, 7.3
Hz, 1H), 5.52 (d, J = 9.7 Hz, 1H), 4.42 ꢀ 4.27 (m, 1H), 4.20 ꢀ 4.05 (m, 1H), 3.69 (br,
1H), 2.38 (s, 3H), 2.32 (s, 3H), 2.23 (s, 3H). 19F NMR (376 MHz, CDCl3) δ ꢀ70.93 (d,
13
J = 7.2 Hz, 3F). C NMR (101 MHz, CDCl3) δ 144.0 (s), 143.3 (s), 138.1 (s), 137.1
(s), 133.6 (s), 133.0 (s), 129.9 (s), 129.8 (s), 129.3 (s), 128.4 (s), 127.1 (s), 126.6 (s),
124.4 (q, J = 283.7 Hz), 124.0 (s), 114.5 (s), 57.38 (q, J = 26.8 Hz), 56.6 (s), 21.5 (s),
21.2 (s), 20.4 (s). IR (neat) ν = 548.9, 667.2, 677.3, 810.5, 919.8, 968.6, 1092.2,
1160.2, 1265.7, 1330.0, 1496.6, 1520.6, 1539.9, 1616.6,2921.6, 3025.2, 3282.6 cmꢀ1.
HRMS (ESI): calcd. for C26H27O2N2F3NaS [M+Na]+: 511.1638. Found: 511.1636.
N-((2S,E)-3-((4-Chlorophenyl)amino)-1,1,1-trifluoro-5-(p-tolyl)pent-4-en-2-yl)-4-
methylbenzenesulfonamide (4e): Yellow solid, 60.1 mg, 59% yield; M.P. 120 ꢀ 122 oC.
1H NMR (400 MHz, CDCl3) δ 7.73 (d, J = 8.2 Hz, 2H), 7.27 ꢀ 7.21 (m, 2H), 7.21 ꢀ
7.15 (m, 2H), 7.14 ꢀ 7.06 (m, 4H), 6.64 ꢀ 6.43 (m, 3H), 5.96 (dd, J = 15.7, 7.7 Hz, 1H),
5.40 (d, J = 9.9 Hz, 1H), 4.39 ꢀ 4.25 (m, 1H), 4.17 ꢀ 4.07 (m, 1H), 3.90 (s, 1H), 2.38 (s,
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3H), 2.32 (s, 3H). 19F NMR (376 MHz, CDCl3) δ ꢀ70.81 (d, J = 6.9 Hz, 3F). 13C NMR
(101 MHz, CDCl3) δ 144.3 (s), 144.2 (s), 138.3 (s), 136.9 (s), 133.9 (s), 132.8 (s),
129.8 (s), 129.3 (s), 129.2 (s), 127.0 (s), 126.6 (s), 124.3 (q, J = 283.7 Hz), 123.6 (s),
123.3 (s), 115.2 (s), 57.4 (q, J = 27.7 Hz), 56.4 (s), 21.5 (s), 21.2 (s). IR (neat) ν =
548.41, 566.40, 666.20, 732.15, 813.83, 911.39, 968.56, 1091.55, 1159.08, 1266.10,
1328.43, 1451.36, 1493.31, 1598.54, 2923.38 cmꢀ1. HRMS (ESI): calcd. for
C25H25O2N2ClF3S [M+H]+: 509.1272. Found: 509.1272.
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enesulfonamide (4f): Yellow liquid, 42.6 mg, 45% yield; 1H NMR (400 MHz, CDCl3)
δ 7.75 (d, J = 8.2 Hz, 2H), 7.24 (d, J = 8.0 Hz, 2H), 7.20 ꢀ7.13 (m, 4H), 7.09 (d, J =
7.9 Hz, 2H), 6.77 (t, J = 7.3 Hz, 1H), 6.63 (d, J = 7.9 Hz, 2H), 6.57 (d, J = 15.7 Hz,
1H), 5.98 (dd, J = 15.9, 7.4 Hz, 1H), 5.38 (d, J = 9.9 Hz, 1H), 4.44 ꢀ 4.33 (m, 1H),
4.20 ꢀ 4.09 (m, 1H), 3.83 (d, J = 7.1 Hz, 1H), 2.38 (s, 3H), 2.32 (s, 3H). 19F NMR
(376 MHz, CDCl3) δ ꢀ70.79 (d, J = 7.4 Hz, 3F). 13C NMR (101 MHz, CDCl3) δ 145.6
(s), 144.1 (s), 138.2 (s), 137.0 (s), 133.9 (s), 132.9 (s), 129.8 (s), 129.4 (s), 129.3 (s),
127.1 (s), 126.6 (s), 124.4 (q, J = 283.7 Hz), 123.6 (s), 119.0 (s), 114.1 (s), 57.2 (q, J
= 28.8 Hz), 56.4 (s), 21.5 (s), 21.2 (s). IR (neat) ν = 549.0, 571.0, 666.1, 690.4, 714.9,
750.2, 812.3, 919.9, 969.0, 1092.7, 1160.2, 1266.2, 1328.3, 1436.5, 1498.5, 1513.3,
1602.2, 2922.1, 3026.8, 3052.0, 3283.1 cmꢀ1. HRMS (ESI): calcd. for
C25H25O2N2F3NaS [M+Na]+: 497.1481. Found: 497.1481.
N-((2S,E)-3-((4-Chlorophenyl)amino)-1,1,1-trifluoro-5-(3-methoxyphenyl)pent-4-e
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n-2-yl)-4-methylbenzenesulfonamide (4g): Yellow liquid, 40.8 mg, 39% yield; H
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NMR (400 MHz, CDCl3) δ 7.72 (d, J = 8.3 Hz, 2H), 7.25 ꢀ 7.16 (m, 3H), 7.09 (d, J =
8.8 Hz, 2H), 6.86 (d, J = 7.7 Hz, 1H), 6.82 ꢀ 6.77 (m, 2H), 6.58 ꢀ 6.51 (m, 3H), 6.00
(dd, J = 15.8, 7.0 Hz, 1H), 5.79 ꢀ 5.65 (m, 1H), 4.42 ꢀ 4.31 (m, 1H), 4.17 ꢀ 4.06 (m,
1H), 3.99 (br, 1H), 3.77 (s, 3H), 2.36 (s, 3H). 19F NMR (376 MHz, CDCl3) δ ꢀ70.93 (d,
J = 6.9 Hz, 3F).13C NMR (101 MHz, CDCl3) δ 159.8 (s), 144.3 (s), 144.3 (s), 137.0
(s), 136.8 (s), 133.8 (s), 129.8 (s), 129.6 (s), 129.2 (s), 127.0 (s), 124.9 (s), 124.2 (q, J
= 283.7 Hz), 123.6 (s), 119.3 (s), 115.2 (s), 113.9 (s), 112.1 (s), 57.5 (q, J = 28.3 Hz),
56.1 (s), 55.2 (s), 21.5 (s). IR (neat) ν = 522.4, 549.2, 568.8, 667.1, 703.9, 814.7,
969.8, 1005.1, 1092.1, 1159.1, 1185.0, 1266.5, 1289.8, 1328.0, 1493.0, 1599.2,
2923.6, 3031.4, 3280.6 cmꢀ1. HRMS (ESI): calcd. for C25H23O3 N2F3ClS [MꢀH]ꢀ:
523.1070. Found: 523.1067.
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N-((2S,E)-5-(4-Chlorophenyl)-1,1,1-trifluoro-3-(phenylamino)pent-4-en-2-yl)-4-me
thylbenzenesulfonamide (4h): Yellow liquid, 62.2 mg, 63% yield; 1H NMR (400 MHz,
CDCl3) δ 7.75 (d, J = 8.1 Hz, 2H), 7.25 ꢀ 7.11 (m, 8H), 6.76 (t, J = 7.3, 1H), 6.62 (d, J
= 8.0 Hz, 2H), 6.54 (d, J = 15.8 Hz, 1H), 6.08 ꢀ 5.97 (m, 2H), 4.47 (br, 1H), 4.23 ꢀ
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4.10 (m, 1H), 4.02 (br, 1H), 2.36 (s, 3H). F NMR (376 MHz, CDCl3) δ ꢀ71.01 (d, J
= 7.2 Hz, 3F). 13C NMR (101 MHz, CDCl3) δ 145.7 (s), 144.2 (s), 136.9 (s), 134.4 (s),
133.8 (s), 132.2 (s), 129.8 (s), 129.4 (s), 128.7 (s), 127.9 (s), 127.0 (s), 125.9 (s),
124.3 (q, J = 284.1 Hz), 119.0 (s), 114.0 (s), 57.5 (q, J = 28.4 Hz), 55.7 (s), 21.5 (s).
IR (neat) ν = 549.0, 570.7, 666.1, 692.6, 750.9, 811.8, 968.4, 994.1, 1092.7, 1159.8,
1265.1, 1328.0, 1436.8, 1492.3, 1559.0, 1602.0, 2924.0, 3054.3, 3281.4 cmꢀ1. HRMS
(ESI): calcd. for C24H21O2N2ClF3S [MꢀH]ꢀ: 493.0964. Found: 493.0965.
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N-((2S,E)-5-(4-Chlorophenyl)-3-((4-chlorophenyl)amino)-1,1,1-trifluoropent-4-en-
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2-yl)-4-methylbenzenesulfonamide (4i): Yellow liquid, 69.8 mg, 66% yield; H NMR
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(400 MHz, CDCl3) δ 7.72 (d, J = 8.3 Hz, 2H), 7.22 ꢀ 7.12 (m, 6H), 7.10 ꢀ 7.04 (m, 2H),
6.54 ꢀ 6.47 (m, 3H), 6.05 (d, J = 9.5 Hz, 1H), 5.99 (dd, J = 16.3, 6.5 Hz, 1H), 4.43 ꢀ
4.36 (m, 1H), 4.18 ꢀ 4.09 (m, 1H), 4.07 (d, J = 9.1 Hz, 1H), 2.35 (s, 3H). 19F NMR
(376 MHz, CDCl3) δ ꢀ71.07 (d, J = 7.2 Hz, 3F). 13C NMR (101 MHz, CDCl3) δ 144.3
(s), 144.2 (s), 136.8 (s), 134.1 (s), 134.0 (s), 132.6 (s), 129.8 (s), 129.3 (s), 128.8 (s),
127.9 (s), 127.0 (s), 125.4 (s), 124.2 (q, J = 284.1 Hz), 123.7 (s), 115.2 (s), 57.5 (q, J
= 28.4 Hz), 56.1 (s), 21.5 (s). IR (neat) ν = 501.96, 548.73, 664.86, 734.58, 813.27,
910.62, 968.00, 1012.62, 1091.48, 1159.19, 1185.11, 1264.87, 1328.55, 1404.26,
1453.88, 1492.41, 1598.33, 2924.10 cmꢀ1. HRMS (ESI): calcd. for C24H22O2N2Cl2F3S
[M+H]+: 529.0726. Found: 529.0726.
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yl)benzenesulfonamide (4j): Yellow liquid, 60.1 mg, 61% yield; H NMR (400 MHz,
CDCl3) δ 7.74 (d, J = 8.2 Hz, 2H), 7.31 ꢀ 7.19 (m, 4H), 7.07 ꢀ 6.90 (m, 4H), 6.65 ꢀ
6.48 (m, 3H), 5.97 (dd, J = 15.6, 7.4 Hz, 1H), 5.42 (d, J = 9.6 Hz, 1H), 4.40 (br, 1H),
4.19 ꢀ 4.04 (m, 1H), 3.81 (d, J = 8.1 Hz, 1H), 2.39 (s, 3H), 2.22 (s, 3H). 19F NMR
(376 MHz, CDCl3) δ ꢀ71.05 (d, J = 7.3 Hz, 3F), ꢀ111.22 ꢀ ꢀ114.99 (m, 1F). 13C NMR
(101 MHz, CDCl3) δ 162.6 (d, J = 247.6 Hz), 144.1 (s), 143.3 (s), 137.1 (s), 132.2 (s),
132.1 (d, J = 3.3 Hz), 129.9 (s), 129.8 (s), 128.4 (s), 128.3 (d, J = 8.1 Hz), 127.0 (s),
125.1 (s), 124.3 (q, J = 284.62 Hz), 115.4 (d, J = 21.7 Hz), 114.4 (s), 57.5 (q, J = 28.1
Hz), 56.2 (s), 21.5 (s), 20.4 (s). IR (neat) ν = 549.1, 586.0, 667.3, 705.3, 811.9, 920.0,
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968.1, 1092.6, 1159.3, 1230.4, 1265.7, 1329.9, 1456.1, 1508.5, 1520.3, 1558.5,
1616.7, 1716.7, 2922.4, 3031.8, 3283.2 cmꢀ1. HRMS (ESI): calcd. for
C25H24O2N2F4NaS [M+Na]+: 515.1387. Found: 515.1387.
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-yl)benzenesulfonamide (4k): Yellow liquid, 56.4 mg, 59% yield; 1H NMR (400 MHz,
CDCl3) δ 7.74 (d, J = 8.1 Hz, 2H), 7.30 ꢀ 7.22 (m, 4H), 7.18 (t, J = 7.8 Hz, 2H), 6.97
(t, J = 8.5 Hz, 2H), 6.77 (t, J = 7.2 Hz, 1H), 6.68 ꢀ 6.52 (m, 3H), 5.99 (dd, J = 15.6,
7.0 Hz, 1H), 5.38 (d, J = 9.9 Hz, 1H), 4.45 ꢀ 4.35 (m, 1H), 4.22 ꢀ 4.07 (m, 1H), 3.83
(d, J = 8.6 Hz, 1H), 2.39 (s, 3H). 19F NMR (376 MHz, CDCl3) δ ꢀ70.97 (d, J = 7.3 Hz,
3F), ꢀ112.48 ꢀ ꢀ114.78 (m, 1F). 13C NMR (101 MHz, CDCl3) δ 162.6 (d, J = 247.6
Hz), 145.7 (s), 144.2 (s), 137.0 (s), 132.3 (s), 132.0 (d, J = 3.3 Hz), 129.8 (s), 129.4
(s), 128.3 (d, J = 8.1 Hz), 127.0 (s), 124.9 (s), 124.3 (q, J = 283.4 Hz), 119.0 (s),
115.5 (d, J = 21.7 Hz), 114.0 (s), 57.6 (q, J = 28.1 Hz), 55.8 (s), 21.5 (s). IR (neat) ν =
548.8, 570.8, 665.7, 691.1, 750.9, 813.0, 919.6, 968.2, 1092.9, 1159.0, 1185.1, 1229.1,
1266.0, 1328.0, 1508.2, 1602.2, 2924.5, 3054.1, 3282.6 cmꢀ1. HRMS (ESI): calcd. for
C24H22O2N2F4NaS [M+Na]+: 501.1230. Found: 501.1231
N-((2S,E)-3-((4-Chlorophenyl)amino)-1,1,1-trifluoro-5-(4-fluorophenyl)pent-4-en-
2-yl)-4-methylbenzenesulfonamide (4l): Yellow solid, 64.5 mg, 63% yield; M.P. 109 ꢀ
1
111 oC. H NMR (400 MHz, CDCl3) δ 7.73 (d, J = 8.3 Hz, 2H), 7.25 ꢀ 7.14 (m, 4H),
7.11 ꢀ 7.04 (m, 2H), 6.93 (t, J = 8.6 Hz, 2H), 6.56 ꢀ 6.49 (m, 3H), 6.01 ꢀ 5.90 (m, 2H),
4.42 ꢀ 4.34 (m, 1H), 4.16 ꢀ 4.09 (m, 1H), 4.05 (d, J = 9.0 Hz, 1H), 2.36 (s, 3H). 19F
NMR (376 MHz, CDCl3) δ ꢀ71.02 (d, J = 7.3 Hz, 3F), ꢀ113.26 ꢀ ꢀ113.35 (m, 1F). 13C
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NMR (101 MHz, CDCl3) δ 162.6 (d, J = 248.0 Hz), 144.3 (s), 136.8 (s), 132.5 (s),
131.9 (d, J = 3.2 Hz), 129.8 (s), 129.2 (s), 128.3 (d, J = 8.1 Hz), 127.0 (s), 124.5 (s),
124.2 (q, J = 283.7 Hz), 123.6 (s), 123.5 (s), 115.5 (d, J = 21.7 Hz), 115.1 (s), 57.64
(q, J = 29.3 Hz), 55.9 (s), 21.5 (s). IR (neat) ν = 548.89, 566.93, 666.25, 733.40,
814.07, 847.17, 910.10, 968.20, 1092.35, 1158.91, 1184.87, 1231.77, 1265.93,
1291.00, 1328.77, 1403.59, 1452.45, 1493.76, 1508.90, 1600.23, 2924.41, 3277.96
cmꢀ1. HRMS (ESI): calcd. for C24H22O2N2ClF4S [M+H]+: 513.1021. Found:
513.1021.
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(E)-N-(3-(butylamino)-1,1,1-trifluoro-5-(p-tolyl)pent-4-en-2-yl)-4-methylbenzenes
ulfonamide (4m): Yellow solid, 45.2 mg, 50% yield; M.P. 71.76 ꢀ 72.31 oC. 1H NMR
(400 MHz, CDCl3) δ 7.74 (d, J = 8.3 Hz, 2H), 7.22 (d, J = 7.9 Hz 2H), 7.15 – 7.09 (m,
4H), 6.47 (d, J = 15.8 Hz, 1H), 5.69 (dd, J = 15.8, 8.8 Hz, 1H), 3.89 (qd, J = 7.9, 2.3
Hz, 1H), 3.59 (dd, J = 8.8, 2.0 Hz, 1H), 2.65 ꢀ 2.40 (m, 2H), 2.36 (s, 3H), 2.33 (s, 3H),
1.41ꢀ 1.35 (m, 2H), 1.32ꢀ 1.25 (m, 2H), 0.87 (t, J = 7.2 Hz, 3H). 19F NMR (376 MHz,
CDCl3) ꢀ72.79 (d, J = 7.9 Hz, 3F). 13C NMR (101 MHz, CDCl3) δ 143.6 (s), 138.0 (s),
137.8 (s), 133.2 (s), 133.1 (s), 129.6 (s), 129.2 (s), 127.0 (s), 126.6 (s), 125.84 (s),
124.6 (q, J = 283.3 Hz), 58.5 (s), 58.1 (q, J = 29.1 Hz), 46.9 (s), 32.1 (s), 21.5 (s),
21.2 (s), 20.2 (s), 13.9 (s). IR (neat) ν = 3333.4, 3025.1, 2985.5, 2930.8, 2863.2,
1598.7, 1468.8, 1353.6, 1273.0, 1171.6, 1134.3, 1094.6, 967.4, 815.9, 800.3, 685.7,
576.2, 561.7, 550.9, 464.1cmꢀ1. HRMS (ESI): calcd. for C23H28O2N2F3S [MꢀH]ꢀ:
453.1829. Found: 453.1829.
Procedure
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5:
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mixture
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(285.1 mg, 1 mmol) and 4Å MS (400 mg) in dichloromethane (5 mL) was added
TBAF (0.75 mL, 1 M in THF) dropwise under N2 atmosphere. The reaction mixture
was stirred at room temperature for 1 h. 4Å MS was removed by filtration. The filtrate
was concentrated to give crude aziridine, into which was added sodium methoxide
(135.1 mg, 2.5 mmol), 15ꢀCrownꢀ5 (110.1 mg, 0.5 mmol) and THF (5 mL) under N2
atmosphere. The reaction mixture was stirred at 80 oC for 2 h. After being cooled to
room temperature, the solution was subjected to flash column chromatography
(petroleum ether : EA = 20:1) to afford the pure product.
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ulfonamide (5a): Yellow solid, 89.8 mg, 45% yield; 1H NMR (400 MHz, CDCl3) δ
7.71 (d, J = 8.2 Hz, 2H), 7.35 ꢀ 7.22 (m, 5H), 7.18 (d, J = 8.0 Hz, 2H), 6.58 (d, J =
15.9 Hz, 1H), 5.82 (dd, J = 15.9, 8.0 Hz, 1H), 5.49 (d, J = 9.3 Hz, 1H), 4.09 (d, J =
8.0 Hz, 1H), 4.04 ꢀ 3.92 (m, 1H), 3.29 (s, 3H), 2.33 (s, 3H). 19F NMR (282 MHz,
CDCl3) δ ꢀ73.34 (d, J = 7.4 Hz, 3F). 13C NMR (101 MHz, CDCl3) δ 143.6 (s), 137.9
(s), 135.5 (s), 135.1 (s), 129.6 (s), 128.6 (s), 128.4 (s), 126.9 (s), 126.9 (s), 124.0 (q, J
= 283.5 Hz), 123.9 (s), 78.0 (q, J = 1.9 Hz), 58.3 (q, J = 30.3 Hz), 56.6 (s), 21.5 (s). IR
(neat) ν = 549.0, 570.1, 660.9, 690.0, 757.5, 844.9, 964.3, 1088.3, 1135.2, 1165.2,
1273.9, 1351.8, 1450.8, 1466.3, 1495.9, 1597.1, 2968.1, 3027.9, 3300.2. HRMS (ESI):
calcd. for C19H19 O3NF3S [MꢀH]ꢀ: 398.1038. Found: 398.1038.
(E)-N-(3-(benzyloxy)-1,1,1-trifluoro-5-phenylpent-4-en-2-yl)-4-methylbenzenesulfo
o
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namide (5b): Yellow solid, 118.7 mg, 50% yield; M.P. 119.8 ꢀ 121.5 C. H NMR
(400 MHz, CDCl3) δ 7.70 (d, J = 8.3 Hz, 2H), 7.39 ꢀ 7.22 (m, 10H), 7.18 (d, J = 8.0
Hz, 2H), 6.58 (d, J = 15.9 Hz, 1H), 5.92 (dd, J = 15.9, 8.2 Hz, 1H), 5.53 (s, 1H), 4.59
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