Concise Asymmetric Synthesis of β-Trifluoromethylated α,β-Diamino Esters through Addition Reactions of Glycine Esters to CF3-Sulfinylimine

Article abstract of DOI:10.1002/ejoc.201301377

(S)-N-(tert-Butylsulfinyl)-3,3,3-trifluoroacetaldimine underwent reactions with enolates of glycine esters with quite remarkable stereochemical results, that is, with virtually complete (>99 % de) diastereoselectivity and excellent (>98 %) yields. Further

Full text of DOI:10.1002/ejoc.201301377

FULL PAPER
DOI: 10.1002/ejoc.201301377
Concise Asymmetric Synthesis of β-Trifluoromethylated α,β-Diamino Esters
through Addition Reactions of Glycine Esters to CF3-Sulfinylimine
Chen Xie,[a] Haibo Mei,[a,b] Lingmin Wu,[a] Vadim A. Soloshonok,[c,d] Jianlin Han,*[a,b] and
Yi Pan*[a]
Keywords: Synthetic methods / Asymmetric synthesis / Diastereoselectivity / Fluorine / Schiff bases
(S)-N-(tert-Butylsulfinyl)-3,3,3-trifluoroacetaldimine under- ationally convenient conditions (Cs2CO3-catalyzed, ambient
went reactions with enolates of glycine esters with quite re-
temperature) to provide the most advanced, general, and
markable stereochemical results, that is, with virtually com- scalable access to biologically important β-trifluoromethyl-
plete (Ͼ99%de) diastereoselectivity and excellent (Ͼ98%)
ated α,β-diamino acids.
yields. Furthermore, the reactions are conducted under oper-
Introduction
actions.[11,12] In particular, the CF3–CH(NH2)– structural
feature is generally used as a pharmacophore in the design
of bioactive compounds, which include α- and β-amino ac-
ids.[13] Considering that naturally occurring diaminobut-
anoic acid has been shown to play a critical role in the bio-
logical activity of various peptide antibiotics, it may be par-
ticularly interesting to study its derivatives, such as its
fluorinated analogue 2,3-diamino-4,4,4-trifluorobutanoic
acid.[14] However, access to enantiomerically pure samples
of 2,3-diamino-4,4,4-trifluorobutanoic acid is rather lim-
ited, as only two literature approaches have been developed
to date. One is the Mannich addition reaction of a chiral
NiII complex of a glycine Schiff base with N-(p-meth-
oxyphenyl)-protected imines, whereas the second involves
the silver-catalyzed 1,3-dipolar cycloaddition of azomethine
ylides with a fluorinated imine.[15] Both approaches share
the drawback of an incomplete stereochemical outcome,
which necessitates tedious chromatographic purifications
and, therefore, renders these methods of limited value for
relatively large-scale synthesis. Herein, we report the ad-
dition reactions between (S)-N-tert-butylsulfinyl-3,3,3-tri-
fluoroacetaldimine (1) and glycine-derived enolates as the
most advanced, convenient, and scalable approach to pre-
pare of β-trifluoromethylated α,β-diamino acids (see
Scheme 1). The reactions were conducted under operation-
ally convenient conditions at ambient temperature to give
the target products with a remarkable stereochemical out-
come (Ͼ99%de, Ͼ98% yield; see Scheme 1). Although the
reaction of glycine esters with a chiral CF3-sulfinylimine
has been reported by Dolbier,[16] the reactions reported in
the patent were conducted at –78 °C in the presence of lith-
ium hexamethyldisilazide (LiHMDS) and gave a mixture of
diastereomers in only 17% chemical yield. Furthermore, the
ratio of the diastereomers, the absolute configuration, and
the mechanism were not discussed or reasonably proved.
α,β-Diamino acids and their derivatives comprise a bio-
logically potent class of naturally occurring amino acids
and have been the focus of multidisciplinary research for
quite some time.[1] Besides their specific biological roles,
α,β-diamino acids that contain two adjacent stereogenic
centers and functional groups serve as key structural inter-
mediates in the pharmaceutical industry and the health sci-
ences.[2] However, the preparation of amino acids that con-
tain two vicinal amino groups is synthetically rather chal-
lenging[3–5] in comparison to the synthesis of regular α-
amino acids[6] or even α-amino-β-hydroxy acids.[7] One of
the most straightforward and generalized approaches to
α,β-diamino acids is through Mannich addition reactions
between properly protected glycine-derived enolates and
imines.[8]
Our interest in the area of biologically important, tailor-
made[9] amines and amino acids is related to the asymmet-
ric synthesis of the corresponding fluorinated derivatives.[10]
Thus, the substitution of hydrogen with fluorine is currently
an established strategy to develop new drugs with improved
metabolic stability, bioavailability, and protein–ligand inter-
[a] School of Chemistry and Chemical Engineering, State of Key
Laboratory of Coordination, Nanjing University,
Nanjing 210093, China
E-mail: hanjl@nju.edu.cn
chem.nju.edu.cn
[b] Institute for Chemistry
University,
& BioMedical Sciences, Nanjing
Nanjing 210093, China
chem.nju.edu.cn
[c] Department of Organic Chemistry I, Faculty of Chemistry,
University of the Basque Country, UPV/EHU,
20018 San Sebastian, Spain
[d] IKERBASQUE, Basque Foundation for Science,
48011 Bilbao, Spain
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201301377.
Eur. J. Org. Chem. 2014, 1445–1451
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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C. Xie, H. Mei, L. Wu, V. A. Soloshonok, J. Han, Y. Pan
FULL PAPER
Scheme 1. Cs2CO3-catalyzed direct addition of imine 1 (THF = tetrahydrofuran).
additional impetus, however, as we expected that the high
C–H acidity of the latter would allow the reactions to be
conducted under operationally convenient conditions[20]
and lead to the development of a truly useful synthetic
method.
Results and Discussion
Our experience with the asymmetric synthesis of various
biologically relevant compounds[17] provided us with an ap-
preciation for the synthetic value of N-sulfinamides as
uniquely potent, versatile, and convenient chiral auxilia-
ries.[8] In particular, (SS)-(N-tert-butylsulfinyl)-3,3,3-tri-
At the outset of this study, we selected glycine methyl
fluoroacetaldimine (1) demonstrates exceptionally high ester 2a as a model substrate to optimize the reaction condi-
CF3-induced reactivity and stereocontrol. Furthermore, the tions (see Table 1). We were delighted to observe that glyc-
commercial availability of imine 1 on a kilogram scale in ine Schiff base 2a underwent a reaction with sulfinylimine
both enantiomeric forms[18] has stimulated vigorous re- 1 at ambient temperature in the absence of a base catalyst.
search activity in the application of this reagent to prepare However, this addition reaction proceeded at quite a slow
biologically important 2,2,2-trifluoroethylamino-containing rate, requiring 48 h to reach completion. The desired prod-
compounds.[18,19] However, all previously reported reactions uct 3a was isolated in 43% yield with a reasonably good
of imine 1 have required the use of an anhydrous solvent, diastereoselectivity (isomer ratio of 100:18:0:0 as deter-
low temperatures (–78 °C), and strong bases, such as lith- mined by 19F NMR analysis; see Table 1, Entry 1). With
ium diisopropylamide (LDA), nBuLi, and LiHMDS. These these results, we planned a systematic study of the reaction
operationally inconvenient conditions present an obvious conditions to achieve a quantitative stereochemical out-
drawback to the application of these procedures. The study come. We found that potassium tert-butoxide and lithium
of reactions between 1 and glycine-derived enolates had an tert-butoxide were very effective at catalyzing the addition
Table 1. Optimization of reaction conditions.[a]
Entry
Catalyst [mol-%]
Solvent
Time [h]
Yield [%][b]
Isomer ratio[c]
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
no catalyst
tBuOK (20)
tBuOLi (20)
CH3ONa (20)
PhONa (20)
NaOH (20)
K2CO3 (20)
Cs2CO3 (20)
TMG[d] (20)
DABCO[d] (20)
Et3N (20)
DCM[d]
DCM
DCM
DCM
DCM
DCM
DCM
DCM
DCM
DCM
DCM
DCM
DCM
CHCl3
THF
48
1
1
24
1
1
24
1
1
24
48
24
1
1
1
1
1
1
1
12
1
12
43
77
78
52
88
90
85
95
93
77
46
41
89
95
97
87
91
91
85
Ͻ20
98
92
100:18:0:0
100:9:0:0
100:7:0:0
100:5:0:39
100:10:0:1
100:14:9:1
100:12:0:1
100:7:0:0
100:7:0:1
100:13:0:1
100:18:0:1
100:15:0:0
100:11:0:0
100:4:0:0
100:1:0:0
100:5:0:0
100:9:0:0
100: 8:0:0
100:76:10:15
–
DMAP[d] (20)
DBU[d] (20)
Cs2CO3 (20)
Cs2CO3 (20)
Cs2CO3 (20)
Cs2CO3 (20)
Cs2CO3 (20)
Cs2CO3 (20)
Cs2CO3 (20)
Cs2CO3 (10)
Cs2CO3 (5)
DMF
CH3CN
toluene
hexane
CH3OH
THF
100:1:0:0
100:3:0:0
THF
[a] Reagents and conditions: sulfinylimine 1 (1.0 mmol), methyl 2-[(diphenylmethylene)amino]acetate (2a; 1.1 mmol), solvent (5 mL).
[b] Isolated yields. [c] Determined by 19F NMR analysis. [d] DCM = dichloromethane, TMG = N,N,NЈ,NЈ-tetramethylguanidine, DABCO
= 1,4-diazabicyclo[2.2.2]octane, DMAP = 4-(dimethylamino)pyridine, DBU = 1,8-diazabicyclo[5.4.0]undec-7-ene.
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Asymmetric Addition Reactions of Glycine Esters to CF3-Sulfinylimine
reaction (room temp., 1 h) and dramatically increased the dependent on the alkyl moiety. The yield and diastereo-
yields and diastereoselectivities of the products (see Table 1, selectivity of the product decreased slightly as the steric
Entries 2 and 3). Several common inorganic and organic bulk of the alkyl group increased (see Table 2, Entries 1–6).
bases were further examined as catalysts. Inorganic bases In contrast, in the case of the aromatic glycine esters, the
were found to be more efficient (see Table 1, Entries 4–8) electronic and steric features of the aromatic ring showed
and gave both higher chemical yields and diastereoselectivi- almost no appreciable effect on the yield and diastereoselec-
ties in comparison to the reactions catalyzed by organic tivity of the product (100:1:0:0 dr for all of these substrates;
bases (see Table 1, Entries 9–13). Among the inorganic see Table 2, Entries 7–17). Notably, the aromatic glycine es-
bases, Cs2CO3 gave the best results in terms of reactivity ters that contained a 1-naphthyl or 2-naphthyl ring (see
and stereoselectivity (see Table 1, Entry 8) to provide the Table 2, Entries 18 and19) also performed well in this reac-
target product 3a in the highest yield and with the highest tion to give the target products in excellent yields (92 and
diastereoselectivity (95% yield, 100:7:0:0 dr). Next, the opti- 91%, respectively) and with only slightly lower diastereo-
mization of the reaction conditions with Cs2CO3 as the cat- selectivities (100:5:0:0).
alyst was the focus, and this was achieved by screening for
To assign the absolute configuration of the two newly
the appropriate solvent (see Table 1, Entries 14–20). Using created stereogenic centers, we performed a crystal structure
CHCl3, THF, or N,N-dimethylformamide (DMF) as the analysis of 3a (see Figure 1). As revealed by the X-ray study,
solvent improved the diastereoselectivity (see Table 1, En- product 3a has the (2S,3S) configuration. The absolute con-
tries 14–16), and THF provided the best results. Further figurations of other products were assigned as (2S,3S) on
optimization efforts showed that the catalyst loading could the basis of the similarities of their spectroscopic and chir-
be lowered to 10 mol-% without any noticeable drop in optical properties.
both the yield and diastereoselectivity (see Table 1, En-
tries 21 and 22).
With the optimized conditions in hand, we then studied
the effect of the glycine ester moiety on the stereochemical
outcome of this reaction (see Table 2). Almost all of the
tested glycine ester substrates worked well under the opti-
mized conditions to afford the corresponding addition
products in both excellent yields and with excellent dia-
stereoselectivities. In the case of the aliphatic glycine esters,
the results indicate that the outcome of the addition was
Figure 1. ORTEP diagram of compound 3a.
Table 2. Reaction scope of glycine ester derivatives.[a]
To account for the observed preference of the products
3 to have the (2S,3S) absolute configuration, we propose
that the studied reactions proceed through an open nonche-
lated transition state (see Scheme 2). Although the nonche-
lated transition state model has been discussed in the litera-
ture,[21] the observed, virtually complete level of stereocon-
trol requires some additional considerations. We believe
that the geometric homogeneity of the glycine enolate might
also play a significant role.[22,23] As shown by the Newman
projection in Scheme 2, besides the intramolecular chela-
Entry
R
Product
Yield [%][b]
Isomer ratio[c]
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
Me
Et
nPr
iPr
tBu
Bn
C6H5
3a
3b
3c
3d
3e
3f
3g
3h
3i
3j
3k
3l
3m
3n
3o
3p
3q
3r
3s
98
97
97
94
94
95
97
93
94
95
98
97
93
92
89
93
89
92
91
100:1:0:0
100:1:0:0
100:1:0:0
100:4:0:0
100:5:0:0
100:4:0:0
100:1:0:0
100:1:0:0
100:1:0:0
100:1:0:0
100:1:0:0
100:1:0:0
100:1:0:0
100:1:0:0
100:1:0:0
100:1:0:0
100:1:0:0
100:5:0:0
100:5:0:0
2-ClC6H4
3-ClC6H4
4-ClC6H4
4-BrC6H4
4-FC6H4
2-MeC6H4
3-MeC6H4
4-MeC6H4
4-MeOC6H4
2,6-Cl2C6H3
1-naphthyl
2-naphthyl
[a] Reagents and conditions: sulfinylimine 1 (1.0 mmol), glycine es-
ters 2 (1.1 mmol), THF (5 mL). [b] Isolated yields. [c] Determined
by 19F NMR analysis.
Scheme 2. Proposed mechanism for the asymmetric addition that
includes a nonchelated transition state and its Newman projection.
Eur. J. Org. Chem. 2014, 1445–1451
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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C. Xie, H. Mei, L. Wu, V. A. Soloshonok, J. Han, Y. Pan
FULL PAPER
Scheme 3. Large-scale application of the reaction.
conducted in a closed system under air and were monitored by
TLC. Flash chromatography was performed with silica gel 60 (200–
300 mesh). Thin layer chromatography was carried out on silica gel
60 F-254 TLC plates (20ϫ20 cm). The 1H NMR spectroscopic
data were recorded with a 400 MHz spectrometer. The chemical
shifts are reported in ppm (δ) relative to tetramethylsilane (TMS: δ
= 0.0 ppm) or to the solvent signal as the internal standard (CHCl3:
δ = 7.26 ppm, relative to TMS). Data are reported as chemical
shift {multiplicity [singlet (s), doublet (d), triplet (t), quartet (q), or
multiplet (m)], coupling constants (Hz), integration}. The 13C
tion of the Cs atom by the enolate, some possible coordina-
tion of the S–O oxygen to the Cs atom may lead to the
additional stabilization of the transition state to give the
(2S,3S)-configured products 3.
The reactions under study have also been explored in
terms of their scalability to a gram-scale synthesis. Gratify-
ingly, an excellent yield (95%) and perfect diastereoselectiv-
ity (isomer ratio of 100:1:0:0) were obtained, as the loading
amount of sulfinylimine 1 was increased from 0.20 to 2.01 g
(see Scheme 3). To our delight, there was practically no de- NMR spectroscopic data were recorded at 101 MHz with complete
proton decoupling. The chemical shifts are reported in ppm (δ)
relative to TMS with the respective solvent resonance as the in-
ternal standard (CDCl3: δ = 77.0 ppm). The 19F NMR spectro-
scopic data (referenced to external CF3COOH) were recorded with
a Bruker ARX 400 MHz spectrometer. The values of the optical
rotations were measured with a Rudolph Automatic Polarimeter
A21101. Infrared spectra were obtained using KBr pellets with a
Bruker Vector 22 instrument. High-resolution mass spectra for all
new compounds were recorded with a Micromass Q-Tof instrument
(ESI).
crease in the yield or diastereoselectivity in comparison to
the 0.20 g scale reaction. This result underscores the prepar-
ative potential of this method for the large-scale prepara-
tion of chiral β-trifluoromethylated α,β-diamino esters,
which are needed in large quantities for the systematic study
of their biological properties.
Finally, considering that these target amino acids might
be useful blocks for peptide synthesis, we briefly studied the
possible selective deprotection of compound 3e. As shown
in Scheme 4, the treatment of 3e with low-concentrated tri-
fluoroacetic acid (TFA) in DCM followed by neutralization
with triethylamine (TEA) allowed for the highly chemose-
lective deprotection of the labile Schiff base function. The
resulting free amine 4e was isolated in good (93%) yield.
Typical Procedure for the Asymmetric Addition of Sulfinylimine:
Sulfinylimine 1 (1.0 mmol), glycine ester 2 (1.1 mmol), and Cs2CO3
(0.1 mmol) were dissolved in THF (5 mL), and the resulting reac-
tion mixture was stirred at room temperature for 1 h. After the
reaction was complete, the mixture was directly applied to silica gel
and purified by flash chromatography to furnish the corresponding
product 3.
Methyl (2S,3S)-3-[(S)-1,1-Dimethylethylsulfinamido]-2-[(diphenyl-
methylene)amino]-4,4,4-trifluorobutanoate (3a): White solid
(467 mg, 0.98 mmol, 98% yield); m.p. 164–165 °C. [α]2D5 = –79.6 (c
1
= 0.82, CHCl3). H NMR (400 MHz, CDCl3): δ = 7.61–7.59 (m, 2
H), 7.45–7.41 (m, 4 H), 7.35 (t, J = 7.5 Hz, 2 H), 7.14–7.11 (m, 2
H), 5.07 (d, J = 10.7 Hz, 1 H), 4.50–4.42 (m, 2 H), 3.72 (s, 3 H),
1.26 (s, 9 H) ppm. 13C NMR (101 MHz, CDCl3): δ = 174.0, 168.9,
138.7, 135.7, 131.2, 129.2, 129.0, 128.8, 128.2, 127.2, 124.4 (q, J =
284.8 Hz), 63.9, 59.7 (q, J = 29.9 Hz), 57.3, 52.8, 22.5 ppm. 19F
Scheme 4. Selective deprotection of functional group.
Conclusions
NMR (376 MHz, CDCl ): δ = –72.5 ppm. IR (KBr): ν = 3336,
˜
3
We have developed a truly practical method to synthesize
a variety of β-trifluoromethylated α,β-diamino esters in
both excellent yields and diastereoselectivities. The reaction
procedure is operationally very simple and requires only
mixing of the reagents and stirring at room temperature for
2956, 1742, 1630, 1449, 1421, 1263, 1254, 1209, 1172, 1140, 1124,
1077, 784, 702, 693 cm–1. HRMS: calcd. for C22H25F3N2O3SNa [M
+ Na]+ 477.1436; found 477.1430.
Ethyl
(2S,3S)-3-[(S)-1,1-Dimethylethylsulfinamido]-2-[(diphenyl-
methylene)amino]-4,4,4-trifluorobutanoate (3b): White solid
1 h. Importantly, this protocol proved to be scalable with- (476 mg, 0.97 mmol, 97% yield); m.p. 71–72 °C. [α]2D5 = –69.1 (c =
0.59, CHCl3). 1H NMR (400 MHz, CDCl3): δ = 7.60 (d, J =
out compromising the stereochemical outcome. Further ap-
plications of imine 1 to the preparation of other chiral
fluorinated amino compounds are under investigation and
will be reported at a later date.
7.4 Hz, 2 H), 7.45–7.43 (m, 4 H), 7.35 (t, J = 7.5 Hz, 2 H), 7.15–
7.13 (m, 2 H), 5.09 (d, J = 10.6 Hz, 1 H), 4.50–4.42 (m, 2 H), 4.16
(q, J = 7.1 Hz, 2 H), 1.27–1.24 (m, 12 H) ppm. 13C NMR
(101 MHz, CDCl3): δ = 173.8, 168.4, 138.7, 135.8, 131.1, 129.1,
128.9, 128.7, 128.2, 127.2, 124.5 (q, J = 284.9 Hz), 63.9, 62.1, 59.7
Experimental Section
(q, J = 29.7 Hz), 57.3, 22.5, 14.1 ppm. 19F NMR (376 MHz,
General Methods: All reagents were obtained from commercial sup-
pliers and used without further purification. The reactions were
CDCl ): δ = –72.5 ppm. IR (KBr): ν = 3509, 3162, 2978, 1744,
˜
3
1622, 1449, 1263, 1211, 1174, 1163, 1148, 1128, 1069, 698 cm–1.
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Asymmetric Addition Reactions of Glycine Esters to CF3-Sulfinylimine
HRMS: calcd. for C23H27F3N2O3SNa [M + Na]+ 491.1592; found 128.3, 127.2, 126.4, 124.5 (q, J = 284.8 Hz), 121.0, 64.0, 59.4 (q,
491.1587.
J = 29.8 Hz), 57.5, 22.7 ppm. 19F NMR (376 MHz, CDCl3): δ =
–72.2 ppm. IR (KBr): ν = 2960, 1767, 1627, 1593, 1492, 1447, 1411,
˜
Propyl (2S,3S)-3-[(S)-1,1-Dimethylethylsulfinamido]-2-[(diphenyl-
methylene)amino]-4,4,4-trifluorobutanoate (3c): White solid
(468 mg, 0.97 mmol, 97% yield); m.p. 89–90 °C. [α]2D5 = –52.4 (c =
0.76, CHCl3). 1H NMR (400 MHz, CDCl3): δ = 7.61–7.59 (m, 2
H), 7.45–7.42 (m, 4 H), 7.37–7.33 (m, 2 H), 7.15–7.12 (m, 2 H),
5.08 (d, J = 10.6 Hz, 1 H), 4.50–4.42 (m, 2 H), 4.12–4.00 (m, 2 H),
1.70–1.58 (m, 2 H), 1.27 (s, 9 H), 0.91 (t, J = 7.4 Hz, 3 H) ppm.
13C NMR (101 MHz, CDCl3): δ = 173.7, 168.4, 138.7, 135.8, 131.1,
129.1, 128.9, 128.7, 128.2, 127.2, 124.5 (q, J = 284.8 Hz), 67.6, 63.8,
59.7 (q, J = 29.7 Hz), 57.3, 22.5, 21.8, 10.4 ppm. 19F NMR
1318, 1292, 1264, 1192, 1165, 1145, 1089, 752, 738, 704, 693 cm–1.
HRMS: calcd. for C27H28F3N2O3S [M + H]+ 517.1773; found
517.1769.
2-Chlorophenyl (2S,3S)-3-[(S)-1,1-Dimethylethylsulfinamido]-2-[(di-
phenylmethylene)amino]-4,4,4-trifluorobutanoate (3h): Colorless oil
(512 mg, 0.93 mmol, 93% yield). [α]2D5 = –26.3 (c = 0.53, CHCl3).
1H NMR (400 MHz, CDCl3): δ = 7.66–7.64 (m, 2 H), 7.49–7.35
(m, 7 H), 7.29–7.17 (m, 4 H), 7.11–7.09 (m, 1 H), 5.27 (d, J =
10.7 Hz, 1 H), 4.84 (d, J = 1.3 Hz, 1 H), 4.71–4.63 (m, 1 H), 1.31
(s, 9 H) ppm. 13C NMR (101 MHz, CDCl3): δ = 174.8, 166.2,
146.5, 138.6, 135.5, 131.4, 130.5, 129.4, 129.0, 128.8, 128.3, 127.9,
127.5, 127.4, 126.4, 124.5 (q, J = 284.8 Hz), 123.0, 63.6, 59.2 (q,
J = 30.0 Hz), 57.6, 22.7 ppm. 19F NMR (376 MHz, CDCl3): δ =
(376 MHz, CDCl ): δ = –72.5 ppm. IR (KBr): ν = 2964, 1725, 1622,
˜
3
1449, 1410, 1316, 1264, 1171, 1146, 1126, 1090, 703 cm–1. HRMS:
calcd. for C24H30F3N2O3S [M + H]+ 483.1929; found 483.1932.
Isopropyl (2S,3S)-3-[(S)-1,1-Dimethylethylsulfinamido]-2-[(diphenyl-
methylene)amino]-4,4,4-trifluorobutanoate (3d): White solid
(454 mg, 0.94 mmol, 94% yield); m.p. 66–68 °C. [α]2D5 = –40.7 (c =
0.65, CHCl3). 1H NMR (400 MHz, CDCl3): δ = 7.62–7.59 (m, 2
H), 7.45–7.41 (m, 4 H), 7.37–7.33 (m, 2 H), 7.15–7.13 (m, 2 H),
5.11 (d, J = 10.6 Hz, 1 H), 5.00 (hept, J = 6.3 Hz, 1 H), 4.49–4.39
(m, 2 H), 1.28–1.19 (m, 15 H) ppm. 13C NMR (101 MHz, CDCl3):
δ = 173.6, 167.8, 138.8, 135.9, 131.1, 129.1, 128.9, 128.6, 128.2,
127.2, 124.5 (q, J = 284.8 Hz), 70.0, 63.9, 59.6 (q, J = 29.7 Hz),
57.3, 22.6, 21.7 (d, J = 4.8 Hz) ppm. 19F NMR (376 MHz, CDCl3):
–72.3 ppm. IR (KBr): ν = 1778, 1628, 1476, 1447, 1291, 1262, 1214,
˜
1175, 1140, 1090, 752, 703, 695 cm–1. HRMS: calcd. for
C27H2735ClF3N2O3S [M + H]+ 551.1383; found 551.1383.
3-Chlorophenyl (2S,3S)-3-[(S)-1,1-Dimethylethylsulfinamido]-2-[(di-
phenylmethylene)amino]-4,4,4-trifluorobutanoate (3i): Colorless oil
(517 mg, 0.94 mmol, 94% yield). [α]2D5 = –68.4 (c = 0.53, CHCl3).
1H NMR (400 MHz, CDCl3): δ = 7.65–7.63 (m, 2 H), 7.52–7.45
(m, 4 H), 7.39–7.35 (m, 2 H), 7.30 (t, J = 8.1 Hz, 1 H), 7.25–7.17
(m, 3 H), 7.05 (t, J = 2.1 Hz, 1 H), 6.95 (dd, J = 8.1, 2.2 Hz, 1 H),
5.20 (d, J = 10.7 Hz, 1 H), 4.72 (s, 1 H), 4.62–4.54 (m, 1 H), 1.29
(s, 9 H) ppm. 13C NMR (101 MHz, CDCl3): δ = 174.8, 166.7,
150.7, 138.4, 135.7, 134.9, 131.4, 130.4, 129.4, 129.0, 128.9, 128.3,
127.1, 126.7, 124.4 (q, J = 284.8 Hz), 121.8, 119.5, 63.9, 59.1 (q,
J = 29.9 Hz), 57.5, 22.6 ppm. 19F NMR (376 MHz, CDCl3): δ =
δ = –72.6 ppm. IR (KBr): ν = 3524, 3338, 3171, 2986, 1744, 1624,
˜
1449, 1263, 1207, 1174, 1163, 1149, 1128, 1103, 1069, 907, 764,
698 cm–1. HRMS: calcd. for C24H30F3N2O3S [M + H]+ 483.1929;
found 483.1924.
tert-Butyl (2S,3S)-3-[(S)-1,1-Dimethylethylsulfinamido]-2-[(diphen-
ylmethylene)amino]-4,4,4-trifluorobutanoate (3e): White solid
(487 mg, 0.94 mmol, 94% yield); m.p. 73–75 °C. [α]2D5 = –28.2 (c =
0.90, CHCl3). 1H NMR (400 MHz, CDCl3): δ = 7.61–7.59 (m, 2
H), 7.47–7.40 (m, 4 H), 7.35–7.32 (m, 2 H), 7.17–7.14 (m, 2 H),
5.16 (d, J = 10.6 Hz, 1 H), 4.46–4.33 (m, 2 H), 1.42 (s, 9 H), 1.30
(s, 9 H) ppm. 13C NMR (101 MHz, CDCl3): δ = 173.3, 167.2,
138.8, 135.9, 131.0, 129.1, 128.8, 128.6, 128.2, 127.2, 124.6 (q, J =
284.8 Hz), 83.0, 64.2, 59.6 (q, J = 29.6 Hz), 57.3, 27.9, 22.7 ppm.
–72.2 ppm. IR (KBr): ν = 3064, 2960, 2928, 2870, 1770, 1627, 1592,
˜
1474, 1447, 1412, 1365, 1318, 1263, 1199, 1175, 1143, 1089, 877,
783, 766, 704, 696, 676 cm–1. HRMS: calcd. for
C27H2735ClF3N2O3S [M + H]+ 551.1383; found 551.1380.
4-Chlorophenyl (2S,3S)-3-[(S)-1,1-Dimethylethylsulfinamido]-2-[(di-
phenylmethylene)amino]-4,4,4-trifluorobutanoate (3j): Colorless oil
(523 mg, 0.95 mmol, 95% yield). [α]2D5 = –85.3 (c = 0.60, CHCl3).
1H NMR (400 MHz, CDCl3): δ = 7.64 (d, J = 7.3 Hz, 2 H), 7.50–
7.44 (m, 4 H), 7.39–7.32 (m, 4 H), 7.19–7.17 (m, 2 H), 7.00–6.98
(m, 2 H), 5.22 (d, J = 10.6 Hz, 1 H), 4.71 (d, J = 0.9 Hz, 1 H), 4.64–
4.56 (m, 1 H), 1.28 (s, 9 H) ppm. 13C NMR (101 MHz, CDCl3): δ
= 174.7, 166.9, 148.8, 138.5, 135.8, 131.8, 131.4, 129.7, 129.4, 129.0,
128.9, 128.3, 127.1, 124.5 (q, J = 284.8 Hz), 122.5, 63.9, 58.9 (q,
J = 29.9 Hz), 57.5, 22.6 ppm. 19F NMR (376 MHz, CDCl3): δ =
19F NMR (376 MHz, CDCl ): δ = –72.7 ppm. IR (KBr): ν = 2979,
˜
3
1728, 1624, 1368, 1294, 1263, 1173, 1152, 1131, 1088, 874, 841,
757, 704 cm–1. HRMS: calcd. for C25H31F3N2O3SNa [M + Na]+
519.1905; found 519.1900.
Benzyl (2S,3S)-3-[(S)-1,1-Dimethylethylsulfinamido]-2-[(diphenyl-
methylene)amino]-4,4,4-trifluorobutanoate (3f):
White solid
(504 mg, 0.95 mmol, 95% yield); m.p. 109–111 °C. [α]2D5 = –51.1 (c
–72.1 ppm. IR (KBr): ν = 2960, 1770, 1627, 1487, 1447, 1318, 1292,
˜
1
= 0.56, CHCl3). H NMR (400 MHz, CDCl3): δ = 7.59–7.57 (m, 2
1264, 1199, 1172, 1143, 1089, 1015, 704, 696 cm–1. HRMS: calcd.
for C27H2735ClF3N2O3S [M + H]+ 551.1383; found 551.1383.
H), 7.46–7.28 (m, 11 H), 7.04–7.02 (m, 2 H), 5.18–5.07 (m, 3 H),
4.50–4.43 (m, 2 H), 1.21 (s, 9 H) ppm. 13C NMR (101 MHz,
CDCl3): δ = 174.0, 168.3, 138.7, 135.7, 134.9, 131.2, 129.1, 129.0,
128.7, 128.6, 128.2, 127.2, 124.5 (d, J = 284.8 Hz), 67.7, 64.0, 59.6
(q, J = 29.8 Hz), 57.3, 22.5 ppm. 19F NMR (376 MHz, CDCl3): δ
4-Bromophenyl (2S,3S)-3-[(S)-1,1-Dimethylethylsulfinamido]-2-[(di-
phenylmethylene)amino]-4,4,4-trifluorobutanoate (3k): White solid
(583 mg, 0.98 mmol, 98% yield); m.p. 121–122 °C. [α]2D5 = –100.8
(c = 0.80, CHCl3). 1H NMR (400 MHz, CDCl3): δ = 7.66–7.61 (m,
2 H), 7.50–7.44 (m, 6 H), 7.37 (t, J = 7.5 Hz, 2 H), 7.20–7.15 (m,
2 H), 6.96–6.90 (m, 2 H), 5.21 (d, J = 10.6 Hz, 1 H), 4.70 (d, J =
1.5 Hz, 1 H), 4.64–4.53 (m, 1 H), 1.28 (s, 9 H) ppm. 13C NMR
= –72.4 ppm. IR (KBr): ν = 3346, 2964, 1748, 1624, 1265, 1189,
˜
1163, 1146, 1129, 1084, 906, 751, 716, 707, 697, 652 cm–1. HRMS:
calcd. for C28H30F3N2O3S [M + H]+ 531.1929; found 531.1924.
Phenyl (2S,3S)-3-[(S)-1,1-Dimethylethylsulfinamido]-2-[(diphenyl-
methylene)amino]-4,4,4-trifluorobutanoate (3g): Colorless oil (101 MHz, CDCl3): δ = 174.7, 166.8, 149.4, 138.4, 135.8, 132.7,
(501 mg, 0.97 mmol, 97% yield). [α]2D5 = –78.8 (c = 0.59, CHCl3).
131.4, 129.4, 129.0, 128.9, 128.3, 127.1, 124.5 (q, J = 284.7 Hz),
1H NMR (400 MHz, CDCl3): δ = 7.65–7.63 (m, 2 H), 7.51–7.44 122.9, 119.5, 63.9, 58.9 (q, J = 29.8 Hz), 57.5, 22.6 ppm. 19F NMR
(m, 4 H), 7.39–7.35 (m, 4 H), 7.26–7.19 (m, 3 H), 7.03–7.00 (m, 2 (376 MHz, CDCl ): δ = –72.1 ppm. IR (KBr): ν = 1750, 1625, 1485,
˜
3
H), 5.20 (d, J = 10.7 Hz, 1 H), 4.72 (d, J = 1.5 Hz, 1 H), 4.65–4.55 1410, 1266, 1204, 1169, 1145, 1128, 1091, 1068, 1012, 879, 765,
(m, 1 H), 1.30 (s, 9 H) ppm. 13C NMR (101 MHz, CDCl3): δ =
174.5, 167.0, 150.4, 138.6, 135.8, 131.4, 129.6, 129.4, 129.0, 128.9,
708, 703, 677 cm–1. HRMS: calcd. for C27H2779BrF3N2O3S [M +
H]+ 595.0878; found 595.0879.
Eur. J. Org. Chem. 2014, 1445–1451
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
1449

C. Xie, H. Mei, L. Wu, V. A. Soloshonok, J. Han, Y. Pan
FULL PAPER
4-Fluorophenyl (2S,3S)-3-[(S)-1,1-Dimethylethylsulfinamido]-2-[(di-
phenylmethylene)amino]-4,4,4-trifluorobutanoate (3l): White solid
(518 mg, 0.97 mmol, 97% yield); m.p. 65–67 °C. [α]2D5 = –72.3 (c =
1
= 0.69, CHCl3). H NMR (400 MHz, CDCl3): δ = 7.66–7.61 (m, 2
H), 7.50–7.44 (m, 4 H), 7.37 (t, J = 7.5 Hz, 2 H), 7.20 (dd, J = 6.5,
3.0 Hz, 2 H), 6.96–6.84 (m, 2 H), 5.20 (d, J = 10.7 Hz, 1 H), 4.70
0.54, CHCl3). 1H NMR (400 MHz, CDCl3): δ = 7.66–7.62 (m, 2 (d, J = 1.5 Hz, 1 H), 4.65–4.54 (m, 1 H), 3.79 (s, 3 H), 1.29 (s, 9
H), 7.52–7.44 (m, 4 H), 7.37 (t, J = 7.5 Hz, 2 H), 7.18 (dd, J = 6.6, H) ppm. 13C NMR (101 MHz, CDCl3): δ = 174.4, 167.3, 157.6,
2.9 Hz, 2 H), 7.08–6.97 (m, 4 H), 5.22 (d, J = 10.6 Hz, 1 H), 4.71
143.8, 138.6, 135.8, 131.3, 129.3, 129.0, 128.9, 128.3, 127.2, 124.5
(d, J = 1.5 Hz, 1 H), 4.65–4.54 (m, 1 H), 1.29 (s, 9 H) ppm. 13C (q, J = 284.9 Hz), 121.8, 114.6, 63.9, 59.4 (q, J = 29.9 Hz), 57.5,
NMR (101 MHz, CDCl3): δ = 174.7, 167.1, 160.4 (d, J = 245.3 Hz),
146.2 (d, J = 2.9 Hz), 138.5, 135.8, 131.4, 129.4, 129.0, 128.9, 128.3,
127.1, 124.5 (q, J = 284.7 Hz), 122.5 (d, J = 8.5 Hz), 116.3 (d, J =
23.6 Hz), 63.9, 59.0 (q, J = 29.9 Hz), 57.5, 22.6 ppm. 19F NMR
55.6, 22.7 ppm. 19F NMR (376 MHz, CDCl3): δ = –72.3 ppm. IR
(KBr): ν = 1766, 1627, 1505, 1446, 1294, 1263, 1191, 1175, 1145,
˜
1092, 1032, 703 cm–1. HRMS: calcd. for C28H30F3N2O4S
[M + H]+ 547.1878; found 547.1880.
(376 MHz, CDCl ): δ = –72.2, –115.9 ppm. IR (KBr): ν = 3331,
˜
3
2,6-Dichlorophenyl (2S,3S)-3-[(S)-1,1-Dimethylethylsulfinamido]-2-
[(diphenylmethylene)amino]-4,4,4-trifluorobutanoate (3q): White so-
lid (520 mg, 0.89 mmol, 89% yield); m.p. 67–69 °C. [α]2D5 = –3.2 (c
2964, 1760, 1629, 1503, 1267, 1184, 1158, 1140, 1080, 1070, 836,
756, 704, 699 cm–1. HRMS: calcd. for C27H27F4N2O3S [M + H]+
535.1679; found 535.1679.
1
= 0.64, CHCl3). H NMR (400 MHz, CDCl3): δ = 7.67–7.63 (m, 2
o-Tolyl (2S,3S)-3-[(S)-1,1-Dimethylethylsulfinamido]-2-[(diphenyl-
methylene)amino]-4,4,4-trifluorobutanoate (3m): Colorless oil
(493 mg, 0.93 mmol, 93% yield). [α]2D5 = –37.5 (c = 0.59, CHCl3).
H), 7.49–7.44 (m, 4 H), 7.39–7.33 (m, 4 H), 7.26–7.24 (m, 2 H),
7.17–7.13 (m, 1 H), 5.27 (d, J = 10.7 Hz, 1 H), 4.94 (d, J = 1.2 Hz,
1 H), 4.72–4.64 (m, 1 H), 1.31 (s, 9 H) ppm. 13C NMR (101 MHz,
1H NMR (400 MHz, CDCl3): δ = 7.67–7.62 (m, 2 H), 7.51–7.43 CDCl3): δ = 175.0, 164.9, 143.3, 138.6, 135.3, 131.4, 129.4, 129.0,
(m, 4 H), 7.37 (t, J = 7.5 Hz, 2 H), 7.23–7.12 (m, 5 H), 6.97–6.93
(m, 1 H), 5.22 (d, J = 10.7 Hz, 1 H), 4.78 (d, J = 1.3 Hz, 1 H),
4.69–4.58 (m, 1 H), 2.03 (s, 3 H), 1.30 (s, 9 H) ppm. 13C NMR
128.8, 128.8, 128.5, 128.3, 127.7, 127.5, 124.4 (q, J = 285.3 Hz),
63.0, 59.6 (q, J = 30.1 Hz), 57.8, 22.8 ppm. 19F NMR (376 MHz,
CDCl ): δ = –72.6 ppm. IR (KBr): ν = 2960, 1789, 1627, 1576,
˜
3
(101 MHz, CDCl3): δ = 174.5, 166.6, 148.9, 138.5, 135.7, 131.4, 1446, 1410, 1292, 1263, 1228, 1177, 1126, 1093, 776, 702, 695 cm–1.
131.3, 129.6, 129.3, 128.9, 128.8, 128.3, 127.3, 127.1, 126.5, 124.5
(q, J = 285.0 Hz), 121.4, 63.6, 59.4 (q, J = 29.8 Hz), 57.5, 22.7,
16.2 ppm. 19F NMR (376 MHz, CDCl3): δ = –72.4 ppm. IR (KBr):
HRMS: calcd. for C27H2635Cl2F3N2O3S [M + H]+ 585.0993; found
585.0996.
Naphthalen-1-yl
(2S,3S)-3-[(S)-1,1-Dimethylethylsulfinamido]-2-
ν = 1770, 1627, 1490, 1447, 1264, 1221, 1171, 1148, 1129, 1109,
˜
[(diphenylmethylene)amino]-4,4,4-trifluorobutanoate (3r): White so-
lid (521 mg, 0.92 mmol, 92% yield); m.p. 60–62 °C. [α]2D5 = +4.0 (c
= 0.61, CHCl3). 1H NMR (400 MHz, CDCl3): δ = 7.86 (d, J =
8.2 Hz, 1 H), 7.77–7.67 (m, 3 H), 7.60–7.36 (m, 10 H), 7.26–7.21
(m, 3 H), 5.27 (d, J = 10.7 Hz, 1 H), 4.95 (d, J = 1.4 Hz, 1 H), 4.78–
4.68 (m, 1 H), 1.28 (s, 9 H) ppm. 13C NMR (101 MHz, CDCl3): δ
1091, 754, 704, 696 cm–1. HRMS: calcd. for C28H30F3N2O3S [M +
H]+ 531.1929; found 531.1930.
m-Tolyl (2S,3S)-3-[(S)-1,1-Dimethylethylsulfinamido]-2-[(diphenyl-
methylene)amino]-4,4,4-trifluorobutanoate (3n): Colorless oil
(488 mg, 0.92 mmol, 92% yield). [α]2D5 = –120.5 (c = 0.54, CHCl3).
1H NMR (400 MHz, CDCl3): δ = 7.65–7.63 (m, 2 H), 7.52–7.44 = 174.7, 167, 146.2, 138.5, 135.8, 134.7, 131.4, 129.4, 129.0, 129.0,
(m, 4 H), 7.37 (t, J = 7.5 Hz, 2 H), 7.26–7.20 (m, 3 H), 7.05 (d, J 128.4, 128.1, 127.4, 126.7, 126.6, 126.3, 125.4, 124.6 (q, J =
= 7.6 Hz, 1 H), 6.85–6.79 (m, 2 H), 5.21 (d, J = 10.7 Hz, 1 H), 4.72
(d, J = 1.6 Hz, 1 H), 4.66–4.55 (m, 1 H), 2.35 (s, 3 H), 1.30 (s, 9
H) ppm. 13C NMR (101 MHz, CDCl3): δ = 174.5, 167.1, 150.3,
139.9, 138.6, 135.8, 131.3, 129.3, 129.3, 129.0, 128.9, 128.3, 127.2,
127.1, 124.5 (q, J = 284.9 Hz), 121.6, 117.9, 64.0, 59.6 (q, J =
29.9 Hz), 57.5, 22.7, 21.3 ppm. 19F NMR (376 MHz, CDCl3): δ =
285.9 Hz), 121.1, 117.7, 63.9, 59.5 (q, J = 29.8 Hz), 57.6, 22.7 ppm.
19F NMR (376 MHz, CDCl ): δ = –72.2 ppm. IR (KBr): ν = 2960,
˜
3
1773, 1627, 1447, 1391, 1291, 1261, 1224, 1174, 1142, 1082, 783,
764, 752, 703, 695 cm–1. HRMS: calcd. for C31H30F3N2O3S [M +
H]+ 567.1929; found 567.1930.
Naphthalen-2-yl
(2S,3S)-3-[(S)-1,1-Dimethylethylsulfinamido]-2-
–72.3 ppm. IR (KBr): ν = 2958, 2927, 1770, 1627, 1616, 1488, 1447,
˜
[(diphenylmethylene)amino]-4,4,4-trifluorobutanoate (3s): White so-
1411, 1290, 1264, 1238, 1172, 1151, 1128, 1090, 704, 696 cm–1.
HRMS: calcd. for C28H30F3N2O3S [M + H]+ 531.1929; found
531.1931.
lid (515 mg, 0.91 mmol, 91% yield); m.p. 83–85 °C. [α]2D5 = –101.7
1
(c = 0.72, CHCl3). H NMR (400 MHz, CDCl3): δ = 7.84 (d, J =
8.7 Hz, 2 H), 7.80–7.76 (m, 1 H), 7.69–7.65 (m, 2 H), 7.53–7.46 (m,
7 H), 7.38 (t, J = 7.5 Hz, 2 H), 7.26–7.22 (m, 2 H), 7.15 (dd, J =
8.9, 2.3 Hz, 1 H), 5.22 (d, J = 10.7 Hz, 1 H), 4.78 (d, J = 1.5 Hz,
1 H), 4.71–4.61 (m, 1 H), 1.31 (s, 9 H) ppm. 13C NMR (101 MHz,
p-Tolyl (2S,3S)-3-[(S)-1,1-Dimethylethylsulfinamido]-2-[(diphenyl-
methylene)amino]-4,4,4-trifluorobutanoate (3o): White solid
(472 mg, 0.89 mmol, 89% yield); m.p. 55–57 °C. [α]2D5 = –85.8 (c =
0.69, CHCl3). 1H NMR (400 MHz, CDCl3): δ = 7.66–7.61 (m, 2 CDCl3): δ = 174.6, 167.2, 148.0, 138.6, 135.8, 133.6, 131.6, 131.3,
H), 7.52–7.43 (m, 4 H), 7.37 (t, J = 7.5 Hz, 2 H), 7.22–7.13 (m, 4
H), 6.89 (d, J = 8.5 Hz, 2 H), 5.19 (d, J = 10.7 Hz, 1 H), 4.71 (d,
J = 1.5 Hz, 1 H), 4.65–4.55 (m, 1 H), 2.33 (s, 3 H), 1.29 (s, 9 H)
ppm. 13C NMR (101 MHz, CDCl3): δ = 174.5, 167.2, 148.2, 138.6,
136.1, 135.8, 131.3, 130.1, 129.3, 129.0, 128.9, 128.3, 127.2, 124.5
(q, J = 284.9 Hz), 120.7, 64.0, 59.5 (q, J = 29.8 Hz), 57.5, 22.7,
20.9 ppm. 19F NMR (376 MHz, CDCl3): δ = –72.3 ppm. IR (KBr):
129.7, 129.4, 129.0, 128.9, 128.3, 127.8, 127.7, 127.3, 126.9, 126.1,
124.5 (d, J = 284.8 Hz), 120.3, 118.2, 64.1, 59.5 (q, J = 29.9 Hz),
57.5, 22.7 ppm. 19F NMR (376 MHz, CDCl3): δ = –72.2 ppm. IR
(KBr): ν = 2978, 1765, 1628, 1446, 1317, 1294, 1262, 1210, 1165,
˜
1152, 1130, 1091, 1077, 746, 700 cm–1. HRMS: calcd. for
C31H30F3N2O3S [M + H]+ 567.1929; found 567.1929.
Procedure for the Selective Deprotection of the Functional Group:
Compound 3e (0.5 mmol) was dissolved in DCM (5 mL) in a reac-
tion vial, and the resulting mixture was cooled to 0 °C. TFA
(1.0 mmol) was added dropwise with stirring, and the reaction was
allowed to continue at 20 °C for 12 h (monitored by TLC). Upon
ν = 3334, 2959, 2927, 1767, 1756, 1627, 1598, 1576, 1506, 1447,
˜
1411, 1318, 1290, 1264, 1214, 1196, 1169, 1146, 1091, 782, 754,
697 cm–1. HRMS: calcd. for C28H30F3N2O3S [M + H]+ 531.1929;
found 531.1928.
4-Methoxyphenyl (2S,3S)-3-[(S)-1,1-Dimethylethylsulfinamido]-2- completion, Et3N (2.0 mmol) was added, and the mixture was
[(diphenylmethylene)amino]-4,4,4-trifluorobutanoate (3p): White so-
stirred at room temp. for 1 h. H2O (10 mL) was then added. The
organic layer was separated, washed with H2O (2ϫ 10 mL), dried
lid (508 mg, 0.93 mmol, 93% yield); m.p. 54–56 °C. [α]2D5 = –89.6 (c
1450
www.eurjoc.org
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2014, 1445–1451

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with anhydrous Na2SO4, and filtered. The solvent was removed to
give the crude product, which was purified by flash chromatog-
raphy.
tert-Butyl
(2S,3S)-2-Amino-3-[(S)-1,1-dimethylethylsulfinamido]-
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4,4,4-trifluorobutanoate (4e): Colorless oil (93% yield). [α]2D5 = –8.2
1
(c = 0.56, CHCl3). H NMR (400 MHz, CDCl3): δ = 4.72 (d, J =
10.4 Hz, 1 H), 4.23–4.10 (m, 1 H), 3.94 (d, J = 1.4 Hz, 1 H), 1.72
(s, 2 H), 1.49 (s, 9 H), 1.21 (s, 9 H) ppm. 13C NMR (101 MHz,
CDCl3): δ = 170.0, 124.8 (q, J = 284.4 Hz), 83.2, 58.7 (q, J =
29.1 Hz), 57.2, 53.1, 28.0, 22.6 ppm. 19F NMR (376 MHz, CDCl3):
δ = –72.99 ppm. IR (KBr): ν = 3390, 3311, 2980, 1739, 1370, 1253,
˜
1156, 1089, 846 cm–1. HRMS: calcd. for C13H23F3N2O3SNa [M +
Na]+ 355.1279; found 355.1280.
Supporting Information (see footnote on the first page of this arti-
cle): Experimental procedures, full spectroscopic data for new com-
1
pounds 3, and copies of H and 13C NMR spectra.
Acknowledgments
We gratefully acknowledge the financial support from the National
Natural Science Foundation of China (No. 21102071) and the Fun-
damental Research Funds for the Central Universities (Nos.
1107020522 and 1082020502). The Jiangsu 333 program (for Y. P.)
and the Changzhou Jin-Feng-Huang program (for J. H.) are also
acknowledged.
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Received: September 11, 2013
Published Online: December 19, 2013
Eur. J. Org. Chem. 2014, 1445–1451
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
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