Optically pure polyfluoroalkanesulfinamides: Synthesis and application as promising and monitorable chiral auxiliaries

Article abstract of DOI:10.1021/jo200119x

Efficient synthesis of enantiopure polyfluoroalkanesulfinamides (PFSAs) has been achieved. Their application as novel chiral auxiliaries with an electron-withdrawing and ¹⁹F NMR monitorable polyfluoroalkyl group was initially demonstrated in an

Full text of DOI:10.1021/jo200119x

NOTE
pubs.acs.org/joc
Optically Pure Polyfluoroalkanesulfinamides: Synthesis and
Application as Promising and Monitorable Chiral Auxiliaries
Li-Juan Liu, Ling-Jun Chen, Peng Li, Xiao-Bo Li, and Jin-Tao Liu*
Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences,
Shanghai 200032, China
S Supporting Information
b
ABSTRACT: Efficient synthesis of enantiopure polyfluoroalkanesulfinamides
(PFSAs) has been achieved. Their application as novel chiral auxiliaries with an
electron-withdrawing and 19F NMR monitorable polyfluoroalkyl group was initially
demonstrated in an asymmetric Strecker reaction under mild conditions.
ecause of the unique properties imparted by fluorine,1
fluoroorganic compounds have seen diverse applications in
Scheme 1. Preparation of
N-Polyfluoroalkanesulfinyloxazolidinones
B
synthetic, agricultural, and medicinal chemistry as well as in
material science.2 Recently, one emerging but still synthetically
challenging area is their application in novel ligand,3 catalyst,4
and chiral auxiliary5 design. Particularly with the few examples of
fluorine-containing chiral auxiliaries, the possibility of monitor-
ing the reaction process and diastereoselectivity by 19F NMR
spectroscopy has rarely been explored.
tert-Butanesulfinamide (TBSA) and p-toluenesulfinamide
(pTSA)6 are widely used as ideal auxiliaries with an electron-
withdrawing sulfinyl group. The chiral alkanesulfinyl group en-
hances the nucleophilicity of the corresponding imine for nucleo-
philic addition. It also provides good diastereofacial selectivity and
is easy to remove from adducts. Nevertheless, additives such as
Lewis acid or base are usually needed to improve the reactivity of
imines. To further enhance the nucleophilicity of the imines and
therefore facilitate the reaction with nucleophiles and extend
the reaction scope, we propose that polyfluoroalkanesulfinamides
(PFSAs) might serve as a superior auxiliary because of the strong
electron-withdrawing effect of polyfluoroalkyl group. In addition,
our previous work has demonstrated the chiral induction potential
of the polyfluoroalkanesulfinyl group due to the steric effect of the
polyfluoroalkyl group in the DielsꢀAlder reaction of N-sulfinyl-
polyfluoroalkanesulfinamides with dienes.7 As part of our ongoing
program aimed at devising novel fluorine-containing chiral aux-
iliaries, we disclose herein the first synthesis of enantiopure
polyfluoroalkanesulfinamides (PFSAs) and demonstrate their
application as novel chiral auxiliaries with an electron-withdrawing
and 19F NMR monitorable polyfluoroalkyl group. The Strecker
reaction was chosen as a demonstration example.
Evans reagent with lithium ammonia.9 Inspired by their work, we
successfully prepared N-polyfluoroalkanesulfinyloxazolidinones
in good yields and diastereoselectivities as shown in Scheme 1.
The major product 3aꢀd could be isolated from the
reaction mixture simply by flash column chromatography or
recrystallization.
Ammonia hydrolysis of 3a with LiHMDS was investigated next
(Table 1). To our delight, the corresponding sulfinamide 4a was
obtained as expected when 3a was added to a solution of LiHMDS
at ꢀ78 °C. The result was quite different from the ring-opening
reaction of (S)-(ꢀ)-1-trifluoromethanesulfinyl-(R)-4-phenylox-
azolin-2-one with dimethylamine, which led to the correspond-
ing 2-amino alcohol.10 Solvent had a dramatic effect on both yield
and enantioselectivity, and dichloromethane gave the best result
among the solvents examined. Initially, an equal amount of
LiHMDS was used, and 4a was obtained in very low yield
(entries 1 and 2). When the amount of LiHMDS was increased
to 2.0 equiv, the yield of 4a was raised to 53%, but lower ee was
obtained (entry 3). To analyze the reason for low ee, the reaction
was quenched at low conversion, and 19F NMR analysis of the
reaction mixture indicated that the diastereoisomer 3a0 was
We envisaged that enantiopure PFSAs could be obtained from
polyfluoroalkanesulfinyl chlorides 1.8 However, because of the
high reactivity of 1, it was difficult to prepare optically pure PFSAs
from 1 directly. Recently, Qin et al. reported the successful synthesis
of TBSA by ammonia hydrolysis of N-tert-butanesulfinyl-substituted
Received: January 22, 2011
Published: April 26, 2011
r
2011 American Chemical Society
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dx.doi.org/10.1021/jo200119x J. Org. Chem. 2011, 76, 4675–4681
|

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NOTE
formed as a byproduct. In view of the SN2 mechanism for the
formation of 4a, it is reasonable to believe that 3a0 was formed
from the reaction of 3a with the lithium salt of 2, which was
produced in situ as illustrated in eq 1. It was the equilibrium
between 3a and 3a0 in the reaction system that resulted in the
racemization of (S)-4a. Therefore, reducing the concentration of
the lithium salt of 2 should be helpful to suppress the formation
of 3a0 and thus improve the ee of the reaction, and an attempt was
made by slowing the addition rate of 3a. As expected, (S)-4a was
obtained in 77% yield and 99% ee when the addition time of 3a
was prolonged to 3 h (entry 6, Table 1). Under the optimized
reaction conditions, optically pure PFSAs 4bꢀd were prepared
in good yield and ee, respectively (entries 9ꢀ11).
Table 1. Synthesis of Optically Pure PFSAs
entry
3
ratioa timeb (h) product
Rf
yieldc (%) eed (%)
1
2
3
4
5
6
7
8
9
3a
3a
3a
3a
3a
3a
3a
1:1
1:1
2:1
2:1
2:1
2:1
2:1
0.5
2.0
0.5
1.0
2.0
3.0
4.0
3.0
3.0
3.0
3.0
(S)-4a ClCF2CF2
(S)-4a ClCF2CF2
(S)-4a ClCF2CF2
(S)-4a ClCF2CF2
(S)-4a ClCF2CF2
(S)-4a ClCF2CF2
(S)-4a ClCF2CF2
(R)-4a ClCF2CF2
(S)-4b CF3CF2
(S)-4c n-C4F9
10
12
53
65
68
77
67
63
67
75
99
95
87
95
96
99
96
93
99
93
99
Taking the Strecker reaction as a demonstration example, we
further explored the application of PFSAs in asymmetric synth-
esis as novel chiral auxiliaries. Strecker reaction11 has been
achieved with good yield and stereoselectivity with TBSA12,13
and pTSA.14ꢀ16 However, expensive Lewis acid, stoichiometric
base, or toxic reagent must be used. Davis and co-workers, who
pioneered the research on sulfinimines, reported that no desired
R-amino nitrile was obtained when Ib derived from pTSA was
treated with TMSCN and CsF in THF. Therefore, they used
ethylaluminum cyanide and isopropyl alcohol as an alternative,
and the corresponding adducts IIb and IIb0 were obtained in 98%
3a0 2:1
3b 2:1
10 3c
2:1
11 3d 2:1
(S)-4d CF3
66
c
a Mole ratio of LiHMDS and 3. b Addition time of 3. Isolated yield.
d Determined by HPLC.
Table 2. Strecker Reaction of 5 with Different Chiral Auxiliaries
entry
imine
R
R0
solvent
T (°C)
time (h)
product
total yield (%)
dea (%)
80
115
2
Ib
5a
5a
5a
5a
5a
5a
5a
5a
5a
5a
Ia
p-tolyl
t-Bu
t-Bu
t-Bu
t-Bu
t-Bu
t-Bu
t-Bu
t-Bu
t-Bu
t-Bu
t-Bu
t-Bu
t-Bu
t-Bu
t-Bu
t-Bu
t-Bu
i-Pr
THF/Et2AlCN
benzene
CH2Cl2
Et2O
ꢀ78
25
25
25
25
25
25
25
25
25
25
25
25
0
IIb, IIb0
6a, 6a0
91
CF2CF2Cl
CF2CF2Cl
CF2CF2Cl
CF2CF2Cl
CF2CF2Cl
CF2CF2Cl
CF2CF2Cl
CF2CF2Cl
CF2CF2Cl
CF2CF2Cl
t-Bu
72
72
72
72
72
12
12
46
9
trace
N.R.
N.R.
N.R.
N.R.
22a
90a
93
3
4
5
THF
6
CH3NO2
MeCN
DMSO
TMU
7
6a, 6a0
6a, 6a0
6a, 6a0
6a, 6a0
6a, 6a0
IIa, IIa0
IIb, IIb0
6a, 6a0
6b, 6b0
6c, 6c0
6d, 6d0
6e, 6e0
6f, 6f0
56
62
76
79
78
58
56
82
80
81
72
62
72
72
8
9
10
11
12
13
14
15
16
17
18
19
20
DMPU
DMF
90a
12
72
72
45
20
36
77
44
70
72
88
DMF
17
Ib
5a
5b
5c
5d
5e
5f
p-tolyl
DMF
49
CF2CF2Cl
CF2CF3
DMF
80
DMF
0
79
n-C4F9
DMF
0
90
CF3
DMF
0
85
CF2CF2Cl
CF2CF2Cl
CF2CF2Cl
DMF
0
75
i-Bu
n-Pr
DMF
0
86
5g
DMF
0
6g, 6g0
79
a Determined by 19F NMR.
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yield with 80% de (Table 2, entry 1).15 But extreme care should
be taken since the reaction is very moisture sensitive. Hou’s
group further demonstrated that the presence of hydrogen at the
R-position of the CdN bond was crucial for the reaction of
imines derived from pTSA with TMSCN and CsF.16 All these
results might be attributed to the low reactivity of imines. Thus,
we supposed that imines derived from PFSAs might be more
reactive and could react with TMSCN under milder conditions.
Therefore, polyfluoroalkanesulfinimines 5aꢀd derived from
pivalaldehyde were prepared as typical substrates, and their
Strecker reactions were investigated. Condition screening indi-
cated that acceptable results could be obtained when the reaction
was carried out in aprotic polar solvents without using any
additives as shown in Table 2 (entries 8ꢀ11). It was reported
that aprotic polar solvents such as DMF and DMSO could serve
as a Lewis base and activate TMSCN because of the interaction
between oxygen atom and silicon atom.17 The efficiency of solvent
correlates with the solvent hydrogen bond basicity.18 It is note-
worthy that the reaction of 5a with TMSCN in DMF afforded 6a
and 6a0 in 88% yield and 78% de at room temperature (entry 11),
comparable to the best result reported with pTSA (entry 1).
To clarify the efficiency of these novel fluorine-containing
auxiliaries, Strecker reactions of Ia and Ib derived from TBSA
and pTSA, respectively, were carried out under similar condi-
tions. Low conversion and poor de were obtained after 3 days as
depicted in Table 2 (entries 12 and 13). Obviously, the presence
of a strong electron-withdrawing polyfluoroalkanesulfinyl group
significantly increased the reactivity of 5a and made the Strecker
reaction take place under very mild conditions. Furthermore, the
reaction progress and stereoselectivity could be conveniently
monitored by 19F NMR spectroscopy during reaction without
workup of the reaction mixture. This simplified our research
greatly and provided a useful tool for the determination of
stereoselectivity of the products. Figure 1 illustrated the consis-
tency between the HPLC and 19F NMR spectra of a mixture of 6a
and 6a0 as a crude product. The diastereomeric ratio between 6a
and 6a0 calculated from 19F NMR spectra is 90.2:9.8, which is
very close to the ratio of 90.6:9.4 determined by HPLC.
Figure 1. HPLC and 19F NMR spectra of the mixture of 6a and 6a0.
Scheme 2. Synthesis of (R)-7a
Further screening reaction conditions showed that up to 82%
de was achieved at 0 °C. Different PFSAs (Table 2, entries
14ꢀ16) gave similar results with the exception that the reaction
of 5d went slower, and relatively lower de was obtained (entry
17). Under the same conditions, 2-chlorotetrafluoroethanesulfi-
nyl-substituted imines 5eꢀg derived from other aldehydes reacted
with TMSCN smoothly to yield the corresponding R-amino
nitriles with good disastereoslectivities (Table 2, entries 18ꢀ20).
To further demonstrate the application of these chiral PFSAs
in asymmetric synthesis, optically pure R-amino nitrile (R)-7a
was prepared from (S)-4a as shown in Scheme 2. No racemiza-
tion was observed during the whole synthetic process as indi-
cated by HPLC analysis of key intermediates. The absolute
configuration of the major product (Ss,Rc)-6a was further proved
by X-ray diffraction analysis (see the Supporting Information).
Compared with tert-butanesulfinyl and p-toluenesulfinyl, the
polyfluoroalkanesulfinyl substituent in 6a was much easier to
remove. Treatment of 6a with 5 N HCl at 50 °C or saturated
HCl/Et2O solution at room temperature for 2 h yielded the
corresponding deprotected amine product 7a. In HCl/Et2O
solution, the racemic polyfluoroalkanesulfinyl residue can be
recycled in the form of sulfinyl chloride simply by filtration of the
reaction mixture. To determine the ee of 7a, a transformation20
to 8a was performed, and 98% ee was achieved.
In summary, optically pure PFSAs were synthesized for the
first time, and their application as promising and 19F NMR
monitorable chiral auxiliaries in asymmetric synthesis was initially
demonstrated. Taking advantage of the strong electron-withdrawing
effect of polyfluoroalkyl group, Strecker reaction of a series of
polyfluoroalkanesulfinimines derived from aldehydes with TMSCN
wasachievedundermildconditionswithgooddiastereoselectivities
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NOTE
without any additives. Furthermore, these fluorine-containing
auxiliaries are easily removed, providing a practical and convenient
method for the synthesis of chiral R-amino nitriles. Moreover, the
presence of the polyfluoroalkyl group made it possible to monitor
the process and stereoselectivities of the reaction conveniently by
19F NMR and thus simplified the research greatly. Further
studies on the application of these polyfluoroalkanesulfinamides
in asymmetric synthesis are in progress in our laboratory.
(Rs,Sc)-4-Phenyl-N-(trifluoromethanesulfinyl)oxazolidin-2-one (3d):
1
mp 109ꢀ112 °C; FT-IR (KBr) 1759, 1197, 775, 706 cmꢀ1; H NMR
(300 MHz, CDCl3) δ (ppm) 7.44ꢀ7.34 (m, 5H), 5.38 (dd, J = 9.1, 4.7
Hz, 1H), 4.86 (dd, J = 9.1, 9.1 Hz, 1H), 4.47 (dd, J = 9.1, 4.7 Hz, 1H); 19
F
NMR (282 MHz, CDCl3) δ (ppm) ꢀ73.18 (s, 3F); 13C NMR (100 MHz,
CDCl3) δ (ppm) 156.2, 137.1, 129.9, 129.5, 127.3, 123.3 (q, J = 179.0 Hz),
74.0, 53.7; EI-MS (m/z) 210 (47), 117 (30), 103 (65), 91 (100), 77 (58);
[R]20 = þ203.0 (c = 0.4, CHCl3). Anal. Calcd for C10H8F3NO3S: C,
D
43.01; H, 2.89; N, 5.02. Found: C, 43.05; H, 3.14; N, 5.03.
(Rs,Sc)-4-Benzyl-N-(2-chlorotetrafluoroethanesulfinyl)oxazolindin-
2-one (3e). Since it is difficult to obtain the single crystal 3aꢀd, 3e
was prepared using the same procedure for the determination of the
absolute configuration of 3 by X-ray diffraction analysis: yield 54%;
white solid; mp 80ꢀ83 °C; FT-IR (KBr) 1785, 1159, 1121 cmꢀ1; 1H
NMR (300 MHz, CDCl3) δ (ppm) 7.35ꢀ7.20 (m, 5H), 4.58ꢀ4.57
(m, 1H), 4.29 (d, J = 5.4 Hz, 2H), 3.40 (d, J = 12.3 Hz, 1H), 2.79 (dd, J =
12.3, 12.3 Hz, 1H); 19F NMR (282 MHz, CDCl3) δ (ppm) ꢀ68.08
(m, 2F), ꢀ110.57 (d, JFF = 221.9 Hz, 1F), ꢀ119.92 (d, JFF = 221.9 Hz,
1F); 13C NMR (100 MHz, CDCl3) δ (ppm) 159.3, 138.3, 133.1, 133.0,
131.6, 125.6 (tt, J = 298.9, 33.0 Hz), 120.4 (ddt, J = 315.2, 313.1, 36.5
Hz), 74.0, 55.4, 42.8 (dd, J = 5.7, 1.8 Hz); HRMS (EI) calcd for
C12H10Cl F4NO3S (Mþ) 359.0006, found 359.0019.
Ammonia Hydrolysis of Polyfluoroalkanesulfinyloxazoli-
dinones. A solution of 3 (0.5 mmol) in CH2Cl2 (7 mL) was added
slowly to a solution of LiHMDS (1.0 mmol) in CH2Cl2 (3 mL) in 3 h at
ꢀ78 °C under the protection of N2. After addition, saturated NH4Cl
(aq) (5 mL) was added immediately. The resulting mixture was extracted
withCH2Cl2 (5 mL ꢁ 3) and driedover Na2SO4. After concentration, the
residue was purified by chromatography on silica gel (EtOAc/petroleum
ether 1/5).
’ EXPERIMENTAL SECTION
General Procedure for the Synthesis of Polyfluoroalkane-
sulfinyloxazolindinones. n-BuLi (2.64 mL, 2.5 M in hexane) was
added dropwise to the solution of 2 (0.978 g, 6 mmol) in THF (30 mL)
at ꢀ78 °C under the protection of N2. After addition, the mixture was
stirred for another 0.5 h. Then polyfluoroalkanesulfinyl chloride (19.8
mmol) in 10 mL of THF was added dropwise. After being stirred for
3 h, the mixture was allowed to warm to room temperature. Solvent
was removed, and the residue was purified by flash chromatography
(EtOAc/petroleum ether 1/7).
(Rs,Sc)-4-Phenyl-N-(2-chlorotetrafluoroethanesulfinyl)oxazolidin-
2-one (3a): white solid; mp 112ꢀ114 °C; FT-IR (KBr) 1786, 1761,
1
803, 757 cmꢀ1; H NMR (300 MHz, CDCl3) δ (ppm) 7.43ꢀ7.36
(m, 5H), 5.35 (dd, J = 9.1, 4.7 Hz, 1H), 4.87 (dd, J = 9.1, 9.1 Hz, 1H),
4.52 (dd, J = 9.1, 4.7 Hz, 1H); 19F NMR (282 MHz, CDCl3) δ (ppm)
ꢀ67.48 (s, 2F), ꢀ108.52 (d, JFF = 223.9 Hz, 1F), ꢀ118.55 (d, JFF
=
223.9 Hz, 1F); 13C NMR (100 MHz, CDCl3) δ (ppm) 155.9, 137.2,
129.8, 129.4, 127.7, 121.8 (tt, J = 298.3, 32.8 Hz), 116.5 (tt, J = 319.1,
36.3 Hz), 73.9, 53.9; EI-MS (m/z) 210 (72), 103 (100), 77 (66);
[R]20D = þ147.2 (c = 0.2, CHCl3). Anal. Calcd for C11H8ClF4NO3S:
C, 38.22; H, 2.33; N, 4.05. Found: C, 38.15; H, 2.44; N, 3.93.
(Ss,Rc)-4-Phenyl-N-(2-chlorotetrafluoroethanesulfinyl)oxazolidin-
2-one (3a0): white solid; mp 110ꢀ112 °C; FT-IR (KBr) 1790, 1765,
(S)-2-Chlorotetrafluoroethanesulfinamide (S)-4a: yield 72%; white
solid; mp 42ꢀ43 °C; FT-IR (KBr) 3238, 3104, 1731, 1561, 1266,
1171 cmꢀ1; 1H NMR (300 MHz, CDCl3) δ (ppm) 4.96 (s, 2H); 19
F
1
803, 757 cmꢀ1; H NMR (300 MHz, CDCl3) δ (ppm) 7.44ꢀ7.36
NMR (282 MHz, CDCl3) δ (ppm) ꢀ67.27 to ꢀ67.32 (m, 2F), ꢀ119.74
(d, JFF = 243.6 Hz, 1F), ꢀ122.47 (d, JFF = 243.6 Hz, 1F); 13C NMR (100
MHz, CDCl3) δ (ppm) 122.4 (tt, J = 298.4, 33.4 Hz), 116.3 (ddt, J =
306.0, 302.0, 35.1 Hz); HRMS (EI) calcd for C2H2ClF4NOS (Mþ)
198.9482, found 198.9480; [R]20D = ꢀ15.5 (c = 1.0, CHCl3, 99% ee).
(R)-2-Chlorotetrafluoroethanesulfinamide (R)-4a: yield 63%; white
solid; mp 41ꢀ43 °C; [R]20D = þ11.4 (c = 0.8, CHCl3, 93% ee).
(S)-Pentafluoroethanesulfinamide (S)-4b: yield 67%; white solid;
mp 35ꢀ36 °C; FT-IR (KBr) 3244, 3115, 1735, 1342, 1216 cmꢀ1; 1H
NMR (300 MHz, CDCl3) δ (ppm) 5.16 (s, 2H); 19F NMR (282 MHz,
CDCl3) δ (ppm) ꢀ79.62 (s, 3F), ꢀ125.14 (d, JFF = 243.6 Hz, 1F),
ꢀ126.34 (d, JFF = 243.6 Hz, 1F); 13C NMR (100 MHz, CDCl3) δ (ppm)
118.0 (ddq, J = 296.2, 32.5, 32.5 Hz), 114.3 (ddt, J = 303.3, 299.6, 38.8
Hz); HRMS (EI) calcd for C2H2F5NOS (Mþ) 182.9777, found
182.9777; [R]20D = ꢀ18.0 (c = 0.6, CHCl3, 99% ee).
(m, 5H), 5.32 (dd, J = 8.9, 4.6 Hz, 1H), 4.87 (dd, J = 8.9, 8.9 Hz, 1H),
4.52 (dd, J = 8.9, 4.6 Hz, 1H); 19F NMR (282 MHz, CDCl3) δ (ppm)
ꢀ67.52 (s, 2F), ꢀ108.54 (d, JFF = 217.1 Hz, 1F), ꢀ118.57 (d, JFF
=
217.1 Hz, 1F); 13C NMR (100 MHz, CDCl3) δ (ppm) 155.9, 137.1,
129.9, 129.5, 127.7, 125.1ꢀ113.1 (m), 74.0, 53.9; EI-MS (m/z) 210
(47), 103 (100), 91 (77), 77 (67); [R]20D = ꢀ280.8 (c = 1.2 ꢁ 10ꢀ2
,
CHCl3). Anal. Calcd for C11H8ClF4NO3S: C, 38.22; H, 2.33; N, 4.05.
Found: C, 38.23; H, 2.49; N, 4.00.
(Rs,Sc)-4-Phenyl-N-(pentafluoroethanesulfinyl)oxazolidin-2-one (3b):
white solid; mp 99ꢀ100 °C; FT-IR (KBr) 1796, 1229, 770, 700 cmꢀ1
;
1H NMR (300 MHz, CDCl3) δ (ppm) 7.44ꢀ7.36 (m, 5H), 5.35 (dd, J =
9.0, 4.8 Hz, 1H), 4.88 (dd, J = 9.0, 9.0 Hz, 1H), 4.53 (dd, J = 9.0, 4.8 Hz,
1H); 19F NMR (282 MHz, CDCl3) δ (ppm) ꢀ79.37 (s, 3F), ꢀ113.74
(d, JFF = 233.2 Hz, 1F), ꢀ122.83 (d, JFF = 233.2 Hz, 1F); 13C NMR (100
MHz, CDCl3) δ (ppm) 155.9, 137.2, 129.9, 129.5, 127.6, 74.1, 53.8;
(S)-Nonafluorobutanesulfinamide (S)-4c: yield 75%; white solid;
mp 64ꢀ66 °C; 1H NMR (300 MHz, CDCl3) δ (ppm) 4.86 (s, 2H); 19
F
EI-MS (m/z) 210 (70), 166 (57), 103 (100), 91 (75), 77 (70); [R]20
=
D
NMR (282 MHz, CDCl3) δ (ppm) ꢀ81.18 to ꢀ81.26 (m, 3F),
ꢀ121.85 to ꢀ122.00 (m, 2F), ꢀ121.84 (dt, J = 243.4, 4.5 Hz, 1F),
ꢀ123.09 (dt, J = 243.4, 4.5 Hz, 1F), ꢀ126.48 to ꢀ126.55 (m, 2F); EI-MS
(m/z) 69 (31), 64 (100); [R]20D = ꢀ6.0 (c = 0.8, CHCl3, 93% ee).
(S)-Trifluoromethanesulfinamide (S)-4d: yield 66%; white solid; mp
þ179.4 (c = 0.2, CHCl3). Anal. Calcd for C11H8F5NO3S: C, 40.13; H,
2.45; N, 4.20. Found: C, 40.10; H, 2.61; N, 4.23.
(Rs,Sc)-4-Phenyl-N-(nonafluorobutanesulfinyl)oxazolidin-2-one (3c):
mp 119ꢀ120 °C; FT-IR (KBr) 1786, 1764, 774, 692 cmꢀ1; 1H NMR
(300 MHz, CDCl3) δ (ppm) 7.41ꢀ7.38 (m, 5H), 5.35 (dd, J = 8.9, 4.7
Hz, 1H), 4.88 (dd, J = 8.9, 8.9 Hz, 1H), 4.53 (dd, J = 8.9, 4.7 Hz, 1H); 19F
NMR (282 MHz, CDCl3) δ (ppm) ꢀ81.25 to ꢀ81.3 (m, 3F), ꢀ109.98
(d, JFF = 234.8 Hz, 1F), ꢀ120.05 (d, JFF = 234.8 Hz, 1F), ꢀ120.50 (d,
JFF = 306.9 Hz, 1F), 122.60 (d, JFF = 306.9 Hz, 1F), ꢀ126.62 to ꢀ126.70
(m, 2F); 13C NMR (100 MHz, CDCl3) δ (ppm) 155.8, 137.1, 129.9,
129.5, 127.8, 121.0ꢀ107.9 (m), 74.0, 54.0; EI-MS (m/z) 210 (45), 103
(100), 91 (84), 77 (68); [R]20D = þ117.2 (c = 0.1, CHCl3). Anal. Calcd
for C13H8F9NO3S: C, 36.37; H, 1.88; N, 3.26. Found: C, 36.25; H, 1.95;
N, 3.21.
1
30ꢀ32 °C; H NMR (300 MHz, CDCl3) δ (ppm) 4.97 (s, 2H); 19F
NMR (282 MHz, CDCl3) δ (ppm) ꢀ80.92 (s, 3F); EI-MS (m/z) 69
(34), 64 (100); [R]20D = ꢀ7.7 (c = 0.1, CHCl3, 99% ee).
General Procedure for the Synthesis of Racemic 4aꢀc. To a
flask containing neat HMDS (16 mL, 0.075 mol) was added 1 (0.075
mol) dropwise at 0 °C. After addition, stirring was continued for 2 h
at room temperature. The TMS-substituted sulfinamide intermediate
was obtained by distillation under reduced pressure (1.0 Torr), which
was further treated with 50 mL of saturated NH4Cl (aq) at room
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The Journal of Organic Chemistry
NOTE
temperature for 2 h. The resulting mixture was extracted with Et2O
(30 mL ꢁ 3) and dried over anhydrous Na2SO4. After concentration
under reduced pressure, the residue was purified by column chroma-
tography (EtOAc/petroleum ether 1/5).
18.4, 18.2; HRMS (ESI) calcd for C6H9ClF4NOS (M þ H)þ 254.0030,
found 254.0024.
2-Chloro-N-(3-methylbutylidene)tetrafluoroethanesulfinamide (5f):
yield 87%; colorless oil; FT-IR (film) 1620 cmꢀ1; 1H NMR (300 MHz,
CDCl3) δ (ppm) 8.29 (t, J = 5.4 Hz), 2.53ꢀ2.38 (m, 2H), 2.13ꢀ1.99 (m,
1H), 0.95 (d, J = 3.0 Hz, 3H), 0.92 (d, J = 2.7 Hz, 3H); 19F NMR (282
MHz, CDCl3) δ (ppm) ꢀ66.36 (s, 2F), ꢀ117.22 (d, JFF = 230.7 Hz, 1F),
ꢀ117.73 (d, JFF = 230.7 Hz, 1F); 13C NMR (100 MHz, CDCl3) δ (ppm)
175.4, 122.2 (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 C7H11ClF4NOS (M þ H)þ
268.0186, found 268.0181.
General Procedure21,22 for the Synthesis of Racemic 4d. A
mixture of CH3CN (600 mL), H2O (600 mL), disodium phosphate
(130.4 g, 0.92 mol), and sodium dithionite (193.2 g, 0.92 mol) was
charged into a 2.0 L autoclave reactor. After the reactor as closed, a
vacuum (20 Torr) was created. Trifluorobromomethane (180 g, 1.2
mol) was then introduced. The mixture was heated to 80 °C and stirred
for 8 h. The resulting mixture was extracted with EtOAc (200 mL ꢁ 4)
and dried over anhydrous Na2SO4. After removal of solvent, a
white solid (40 g) was obtained, which was further treated with
thionyl chloride and HMDS in sequence at ꢀ20 °C, and the resulting
mixture was stirred at ꢀ10 °C for 3 h. Purification by flash column
chromatography (EtOAc/petroleum ether 1/5) gave a colorless oil. Total
yield: 25%.
2-Chloro-N-(n-butylidene)tetrafluoroethanesulfinamide (5g): yield
1
76%; colorless oil; FT-IR (film) 1622 cmꢀ1; H NMR (300 MHz,
CDCl3) δ (ppm) 8.36 (t, J = 4.5 Hz, 1H), 2.59 (dt, J = 7.4, 4.5 Hz, 2H),
1.76ꢀ1.63 (m, 2H), 0.98 (t, J = 7.4 Hz, 3H); 19F NMR (282 MHz,
CDCl3) δ (ppm) ꢀ66.39 (s, 2F), ꢀ117.62 (s, 2F); 13C NMR (125
MHz, CDCl3) δ (ppm) 175.4, 122.0 (tt, J = 373.8, 45.6 Hz), 116.6(tt, J =
387.5, 45.6 Hz), 38.4, 18.3,13.4; HRMS (ESI) calcd for C6H9ClF4NOS
(M þ H)þ 254.0030, found 254.0024.
General Procedure for the Synthesis of Sulfinimines. To a
10 mL reaction tube charged with PFSAs (3.0 mmol), titanium(IV)
isopropoxide (4.5 mmol), and CH2Cl2 (3.0 mL) was added aldehyde
(3.0 mmol). The mixture was stirred at room temperature and mon-
itored by TLC. After completion, brine (5 mL) was added, and the
resulting mixture was filtered through Celite. The filter cake was washed
with CH2Cl2. The aqueous phase was extracted with CH2Cl2 (5.0 mL ꢁ
3), and the combined organic phase was dried over anhydrous Na2SO4.
After concentrated, the residue was purified by flash column chroma-
tography (EtOAc/petroleum ether: 1/20).
2-Chloro-N-(2,2-dimethylpropylidene)tetrafluoroethanesulfinamide
(5a): yield 85%; colorless oil; FT-IR (film) 1717 cmꢀ1; 1H NMR (300
MHz, CDCl3) δ (ppm) 8.15 (s, 1H), 1.08 (s, 9H); 19F NMR (282 MHz,
CDCl3) δ (ppm) ꢀ67.78 (s, 2F), ꢀ118.74 (d, JFF = 234.6 Hz, 1F),
ꢀ121.03 (d, JFF = 234.6 Hz, 1F); 13C NMR (100 MHz, CDCl3) δ (ppm)
181.3, 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 C7H11ClF4NOS (M þ H)þ 268.0186,
found 268.0181.
General Procedure for the Strecker Reaction. To a solution
of polyfluoroalkanesulfinimine (0.5 mmol) in anhydrous DMF (1.0 mL)
was added TMSCN (1.0 mmol) dropwise via a syringe at 0 °C. The
resulting mixture was stirred at 0 °C and monitored by 19F NMR. After
completion, the mixture was quenched with brine (5 mL) and extracted
with Et2O (5 mL ꢁ 3). The combined organic phase was washed with
water (1 mL ꢁ 3) and dried over anhydrous Na2SO4. After concentra-
tion, the residue was purified by column chromatography (EtOAc/
petroleum ether: 1/20) to give the corresponding products.
(()-(Rc,Ss)-1-(tert-Butylsulfinylamino)-2,2-dimethylbutyronitrile
1
(IIa): white solid; mp 89ꢀ90 °C; FT-IR (KBr) 3214, 2245 cmꢀ1; H
NMR (300 MHz, CDCl3) δ (ppm) 3.78 (d, J = 9.9 Hz, 1H), 3.70 (d, J =
9.9 Hz, 1H), 1.25 (s, 9H), 1.07 (s, 9H); 13C NMR (100 MHz, CDCl3) δ
(ppm) 118.5, 57.4, 56.7, 35.8, 25.8, 22.7; EI-MS (m/z) 57 (100). Anal.
Calcd for C10H20N2OS: C, 55.52; H, 9.32; N, 12.95. Found: C, 55.68; H,
9.40; N, 12.98.
(()-(Sc,Ss)-1-(tert-Butylsulfinylamino)-2,2-dimethylbutyronitrile
(IIa0): colorless oil; FT-IR (film) 3224, 2240 cmꢀ1; 1H NMR (300 MHz,
CDCl3) δ (ppm) 3.96 (dd, J = 6.6, 2.0 Hz, 1H), 3.52 (d, J = 6.6 Hz, 1H),
1.24 (d, J = 2.1 Hz, 9H), 1.10 (d, J = 2.1 Hz, 9H); 13C NMR (100 MHz,
CDCl3) δ (ppm) 117.9, 58.5, 57.0, 35.4, 25.9, 22.3; EI-MS (m/z) 57
(100). Anal. Calcd for C10H20N2OS: C, 55.52; H, 9.32; N, 12.95. Found:
C, 55.59; H, 9.45; N, 12.91.
N-(2,2-Dimethylpropylidene)pentafluoroethanesulfinamide (5b):
yield 82%; colorless oil; FT-IR (film) 1707 cmꢀ1; 1H NMR (300 MHz,
CDCl3) δ (ppm) 8.21 (s, 1H), 1.20 (s, 9H); 19F NMR (282 MHz,
CDCl3) δ (ppm) ꢀ78.70 (s, 3F), ꢀ120.87 (d, JFF = 242.0 Hz, 1F),
ꢀ124.32 (d, JFF = 242.0 Hz, 1F); 13C NMR (100 MHz, CDCl3) δ (ppm)
181.7, 123.0ꢀ112.5 (m), 39.2, 26.2; HRMS (EI) calcd for C6H10F3NOS
(Mþ) 201.0435, found 201.0428.
(()-(Rc,Ss)-1-(p-Toluenesulfinylamino)-2,2-dimethylbutyronitrile
(IIb): 1H NMR (300 MHz, CDCl3) δ (ppm) 7.59 (d, J = 7.5 Hz, 2H),
7.33 (d, J = 7.5 Hz, 2H), 4.84 (d, J = 10.2 Hz, 1H), 3.54 (d, J = 10.2 Hz,
1H), 2.42 (s, 3H), 1.09 (s, 9H); EI-MS (m/z) 250 (Mþ, 4), 156 (100).
(()-(Sc,Ss)-1-(p-Toluenesulfinylamino)-2,2-dimethylbutyronitrile
(IIb0): 1H NMR (300 MHz, CDCl3) δ (ppm) 7.59 (d, J = 7.5 Hz, 2H),
7.33 (d, J = 7.5 Hz, 2H), 4.68 (d, J = 9.0 Hz, 1H), 3.81 (d, J = 9.0 Hz, 1H),
2.42 (s, 3H), 1.09 (s, 9H); EI-MS (m/z) 250 (Mþ, 4), 156 (100).
(()-(Rc,Ss)-1-(2-Chlorotetrafluoroethanesulfinylamino)-2,2-dimethy-
lbutyronitrile (6a): white solid; mp 80ꢀ81 °C; FT-IR (KBr) 3207,
2245 cmꢀ1; 1H NMR (300 MHz, CDCl3) δ (ppm) 5.15 (d, J = 9.6 Hz,
1H), 4.06 (d, J = 9.6 Hz, 1H), 1.14 (d, J = 2.7 Hz, 9H); 19F NMR (282
MHz, CDCl3) δ (ppm) ꢀ67.73 (s, 2F), ꢀ115.17 (d, JFF = 230.7, 1F),
ꢀ122.55 (d, JFF = 230.7, 1F); 13C NMR (100 MHz, CDCl3) δ (ppm)
122.0 (tt, J = 281.1, 33.0 Hz), 116.4 (tt, J = 309.6, 39.6 Hz), 117.0, 55.9,
35.8, 25.6; MS (ESI) (M þ NH4)þ 312. Anal. Calcd for C8H11ClF4N2OS:
C, 32.60; H, 3.76; N, 9.51. Found: C, 32.89; H, 3.99; N, 9.51.
(Rc,Ss)-6a: white solid; yield 77%; [R]28D = þ35.0 (c = 0.1, CHCl3,
99% ee).
N-(2,2-Dimethylpropylidene)nonafluorobutanesulfinamide (5c):
colorless oil; FT-IR (film) 1619 cmꢀ1; 1H NMR (300 MHz, CDCl3) δ
(ppm) 8.23 (s, 1H), 1.20 (s, 9H); 19F NMR (282 MHz, CDCl3)
δ (ppm) ꢀ81.15 to ꢀ81.22 (m, 3F), ꢀ114.48 (d, JFF = 243.6, 1F),
ꢀ121.69 (d, JFF = 243.6, 1F), ꢀ121.71 to ꢀ121.79 (m, 2F), ꢀ116.89 (d,
JFF = 296.1 Hz, 1F), ꢀ123.31 (d, JFF = 296.1 Hz, 1F); 13C NMR (100
MHz, CDCl3) δ (ppm) 181.7, 122.2ꢀ105.7 (m), 39.2, 26.2; HRMS
(EI) calcd for C5HF9NOS (M ꢀ C4H9)þ 293.9635, found 293.9634.
N-(2,2-Dimethylpropylidene)trifluoromethanesulfinamide (5d):
yield 71%; colorless oil; FT-IR (film) 1707 cmꢀ1 1H NMR (300
;
MHz, CDCl3) δ (ppm) 8.21 (s, 1H), 1.20 (s, 9H); 19F NMR (282
MHz, CDCl3) δ (ppm) ꢀ77.15 (s, 3F); 13C NMR (100 MHz, CDCl3)
δ (ppm) 181.5, 123.8 (q, J = 332.2 Hz), 39.1, 26.5; HRMS (EI) calcd for
C6H10F3NOS (M)þ 201.0435, found 201.0428.
2-Chloro-N-(2-methylpropylidene)tetrafluoroethanesulfinamide
(5e): yield 76%; colorless oil; FT-IR (film) 1624 cmꢀ1; 1H NMR (300
MHz, CDCl3): δ (ppm) 8.28 (d, J = 4.2 Hz, 1H), 2.85ꢀ2.74 (m, 1H),
1.19 (d, J = 3.9 Hz, 3H), 1.18 (d, J = 3.0 Hz, 3H); 19F NMR (282 MHz,
CDCl3) δ (ppm) ꢀ65.88 (s, 2F), ꢀ116.77 (d, JFF = 230.4 Hz, 1F),
ꢀ117.91 (d, JFF = 230.4 Hz, 1F); 13C NMR (100 MHz, CDCl3) δ (ppm)
179.2, 122.2 (tt, J = 299.2, 32.7 Hz), 116.6, (tt, J = 270.6, 36.5 Hz), 35.7,
(()-(Rc,Ss)-1-(Pentafluoroethanesulfinylamino)-2,2-dimethylbu-
tyronitrile (6b): white solid; mp 91ꢀ92 °C; FT-IR (KBr) 3273,
2267 cmꢀ1; 1H NMR (300 MHz, CDCl3) δ (ppm) 4.77 (d, J = 9.9 Hz,
4679
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The Journal of Organic Chemistry
NOTE
1H), 4.06 (d, J = 9.9 Hz, 1H), 1.16 (s, 9H); 19F NMR (282 MHz,
CDCl3) δ (ppm) ꢀ78.88 (s, 3F), ꢀ119.99 (d, JFF = 233.1 Hz, 1F),
ꢀ125.69 (d, JFF = 233.1 Hz, 1F); 13C NMR (100 MHz, CDCl3) δ (ppm)
122.9ꢀ112.4 (m), 117.2, 56.2, 36.0, 25.8; EI-MS (m/z) 159 (50),
96 (74), 57 (100). Anal. Calcd for C8H11F5N2OS: C, 34.53; H, 3.98; N,
10.07. Found: C, 34.56; H, 3.99; N, 10.03.
(()-(Sc,Ss)-1-(2-Chlorotetrafluorosulfinylamino)-3-methylpenta-
nenitrile (6f0):white solid;mp54ꢀ55°C;FT-IR (KBr) 3240, 2552cmꢀ1
;
1H NMR (300 MHz, CDCl3) δ (ppm) 4.95 (d, J = 8.7 Hz, 1H), 4.48 (dd,
J = 16.1, 7.8 Hz, 1H), 1.91ꢀ1.71 (m, 3H), 1.02 (d, J = 6.3 Hz, 3H), 0.98
(d, J = 6.6 Hz, 3H); 19F NMR (282 MHz, CDCl3) δ (ppm) ꢀ66.71 (m,
2F), ꢀ113.31 (d, JFF = 232.7 Hz, 1F), ꢀ119.41 (d, JFF = 232.7 Hz, 1F);
13C NMR (100 MHz, CDCl3) δ (ppm) 121.7 (tt, J = 214.4, 33.0 Hz),
118.7, 116.5 (tt, J = 307.0, 35.4 Hz), 43.8, 40.9, 24.5, 21.8, 21.6; HRMS
(ESI) calcd for C8H11ClF4N2NaOS (M þ Na)þ 317.0114, found
317.0109. Anal. Calcd for C8H11ClF4N2OS: C, 32.60; H, 3.76; N, 9.51.
Found: C, 32.67; H, 3.89; N, 9.51.
(()-(Sc,Ss)-1-(Pentafluoroethanesulfinylamino)-2,2-dimethylbutyro-
nitrile (6b0): white solid; mp 71ꢀ73 °C; FT-IR (KBr) 3261, 2252 cmꢀ1
;
1H NMR (300 MHz, CDCl3) δ (ppm) 5.23 (s, 1H), 4.13 (s, 1H), 1.11 (s,
9H); 19F NMR (282 MHz, CDCl3) δ (ppm) ꢀ79.11 (s, 3F), ꢀ118.01 (d,
JFF = 243.4 Hz, 1F), ꢀ124.15 (d, JFF = 243.4 Hz, 1F); 13C NMR (100
MHz, CDCl3) δ (ppm) 117.1, 53.4, 35.9, 25.9; HRMS (EI) calcd for
C6H11N2OS (M-C2F5)þ 159.0592, found 159.0593.
(()-(Rc,Ss)-1-(2-Chlorotetrafluorosulfinylamino)pentanenitrile (6g):
white solid; mp 64ꢀ65 °C; FT-IR (KBr) 3192, 2245 cmꢀ1 ; 1H NMR
(300 MHz, CDCl3) δ (ppm) 5.21 (d, J = 8.4 Hz, 1H), 4.39 (dd, J = 15.3,
8.1 Hz, 1H), 1.97ꢀ1.85 (m, 2H), 1.64ꢀ1.52 (m, 2H), 1.01 (t, J = 7.2 Hz,
3H); 19F NMR(282 MHz, CDCl3) δ(ppm) ꢀ67.59 (s, 2F), ꢀ115.54 (d,
JFF = 231.7 Hz, 1F), ꢀ120.59 (d, JFF = 231.7 Hz, 1F); 13C NMR (100
MHz, CDCl3) δ (ppm) 121.8 (tt, J = 298.8, 33.1 Hz), 118.1, 116.5 (tt,
J = 307.5, 35.8 Hz), 44.4, 36.9, 18.6, 13.0; HRMS (ESI) calcd for C7H9-
ClF4N2OS (Mþ) 252.9951, found 252.9952. Anal. Calcd for C7H9ClF4-
N2OS: C, 29.95; H, 3.23; N, 9.98. Found: C, 29.98; H, 3.23; N, 9.82.
Removal of Chiral Auxiliary. Method A. To a 10 mL round-
bottom flask equipped with a reflux condenser were added (Ss,Rc)-6a
(50 mg, 0.17 mmol), 5 N HCl (0.34 mL), and MeOH (0.34 mL). The
mixture was stirred at 50 °C and monitored by TLC. After completion of
the reaction, the mixture was cooled to room temperature, adjusted to
pH = 10 with 2 M NaOH, and then extracted with EtOAc (1.0 mL ꢁ 5).
Dry hydrogen chloride was bubbled through the combined organic
solution for 5 min, and a white solid precipitated. Evaporation of the
volatile solvent under reduced pressure afforded 24.7 mg (98% yield) of
(R)-7a:19 [R]25D = þ12.2 (c = 0.6, MeOH); 1H NMR (300 MHz, D2O)
δ (ppm) 0.22 (s, 9H), 3.42 (s, 1H).
(()-(Rc,Ss)-1-(Nonafluorobutanesulfinylamino)-2,2-dimethylbutyro-
nitrile (6c): white solid; mp 93ꢀ94 °C; FT-IR (KBr) 3308, 2244 cmꢀ1
;
1H NMR (300 MHz, CDCl3) δ (ppm) 4.91 (d, J = 9.3 Hz, 1H), 4.06 (d,
J = 9.3 Hz, 1H), 1.16 (s, 9H); 19F NMR (282 MHz, CDCl3) δ (ppm)
ꢀ81.09 to ꢀ81.15 (m, 3F), ꢀ116.89 (dt, J = 247.6, 12.0 Hz, 1F), ꢀ121.96
to ꢀ122.07 (m, 2F), ꢀ123.31 (dt, J = 247.6, 12.0 Hz, 1F), ꢀ125.41 to
ꢀ127.68 (m, 2F); 13C NMR (100 MHz, CDCl3) δ (ppm) 117.2, 56.3,
36.1, 25.8; EI-MS (m/z) 159 (54), 96 (81), 57 (100). Anal. Calcd for
C10H11F9N2OS: C, 31.75; H, 2.93; N, 7.41. Found: C, 31.69; H, 2.94;
N, 7.32.
(()-(Sc,Ss)-1-(Nonafluorobutanesulfinylamino)-2,2-dimethylbutyr-
onitrile (6c0): white solid; mp 89ꢀ90 °C; FT-IR (KBr) 3298,
1
2244 cmꢀ1; H NMR (300 MHz, CDCl3) δ (ppm) 5.09 (d, J = 9.6
Hz, 1H), 4.17 (d, J = 9.9 Hz, 1H), 1.11 (s, 9H); 19F NMR (282 MHz,
CDCl3) δ (ppm) ꢀ81.16 (s, 3F), ꢀ114.48 (d, JFF = 249.6 Hz, 1F),
ꢀ121.69 (d, JFF = 249.6 Hz, 1F), ꢀ122.08 (s, 2F), ꢀ126.59 (s, 2F); 13
C
NMR (100 MHz, CDCl3) δ (ppm) 117.0, 52.7, 35.9, 25.9; HRMS (EI)
calcd for C6H2F9N2OS (M ꢀ C4H9)þ 320.9744, found 320.9746.
(()-(Rc,Ss)-1-(Trifluoromethanesulfinylamino)-2,2-dimethylbu-
tyronitrile (6d): white solid; mp 63ꢀ64 °C; FT-IR (KBr) 3297,
Method B. To a 10 mL round-bottom flask were added (Ss,Rc)-6a
(50 mg, 0.17 mmol) and saturated HCl/Et2O (1.0 mL), and a white
solid precipitated. After 2 h, the reaction mixture was filtrated and
washed with diethyl ether (1.0 mL ꢁ 2) to give the corresponding
product (R)-7a as a white solid.
1
2237 cmꢀ1; H NMR (300 MHz, CDCl3) δ (ppm) 4.86 (d, J = 9.6
Hz, 1H), 4.05 (d, J = 9.6 Hz, 1H), 1.15 (s, 9H); 19F NMR (282 MHz,
CDCl3) δ (ppm) ꢀ77.85 (s, 3F); 13C NMR (100 MHz, CDCl3) δ
(ppm) 123.8 (q, J = 332.7 Hz), 117.6, 54.9, 35.9, 25.9; HRMS (EI) calcd
for C3H2F3N2OS (M ꢀ C4H9)þ 170.9840, found 170.9844.
Determination of ee of (R)-7a. To the solution of benzaldehyde
(11.7 mg, 0.11 mmol) in CH2Cl2 (1 mL) were added MgSO4 (43.2 mg,
0.36 mmol), (R)-7a (17.8 mg, 0.12 mmol), and Et3N (10.1 mg, 0.1
mmol). After the mixture was stirred overnight at room temperature,
MgSO4 was removed by filtration, and the solvent was removed in
vacuum. The residue was purified by flash column chromatography
(()-(Sc,Ss)-1-(Trifluoromethanesulfinylamino)-2,2-dimethylbu-
tyronitrile (6d0): colorless oil; FT-IR (film) 3262, 2259 cmꢀ1; 1H NMR
(300 MHz, CDCl3) δ (ppm) 5.23 (s, 1H), 4.13 (s, 1H), 1.11 (s, 9H); 19
F
NMR (282 MHz, CDCl3) δ (ppm) ꢀ76.33 (s, 3F); 13C NMR (100
MHz, CDCl3) δ (ppm) 123.8 (q, J = 337.8 Hz), 117.1, 54.4, 35.7, 25.9;
HRMS (EI) calcd for C6H11N2OS (M-CF3)þ 159.0592, found 159.0591.
(()-(Rc,Ss)-1-(2-Chlorotetrafluorosulfinylamino)-2-methylbutyr-
(EtOAc/petroleum ether, 1/20) to give (R)-8a: yield 73%; [R]26
=
D
þ19.2 (c = 1.0, CHCl3, 98% ee); 1H NMR (300 MHz, CDCl3) δ (ppm)
8.47 (s, 1H), 7.82ꢀ7.80 (m, 2H), 7.46ꢀ7.45 (m, 3H), 4.32 (d, J = 1.2
Hz, 1H), 1.13 (d, J = 3.6 Hz, 9H).
onitrile (6e): white solid; mp 41ꢀ42 °C; FT-IR (KBr) 3208, 2243 cmꢀ1
;
1H NMR (300 MHz, CDCl3) δ (ppm) 5.39 (d, J = 8.7 Hz, 1H), 4.24 (dd,
J = 8.7, 6.0 Hz, 1H), 2.21ꢀ2.10 (m, 1H), 1.15 (d, J = 5.1 Hz, 3H), 1.13
(d, J = 5.4 Hz, 3H); 19F NMR (282 MHz, CDCl3) δ (ppm) ꢀ67.68
(m, 2F), ꢀ115.51 (d, JFF = 231.0 Hz, 1F), ꢀ121.22 (d, JFF = 231.0 Hz,
1F); 13C NMR (100 MHz, CDCl3) δ (ppm) 121.8 (tt, J = 298.8, 33.4
Hz), 117.0, 116.5(tt, J = 308.1, 35.5Hz), 50.8, 32.6, 18.6, 17.5; EI-MS (m/
z) 145 (59), 82 (100), 43 (24). Anal. Calcd for C7H9ClF4N2OS: C, 29.95;
H, 3.23; N, 9.98. Found: C, 30.20; H, 3.34; N, 9.91.
’ ASSOCIATED CONTENT
S
Supporting Information. NMR spectra of all new com-
b
pounds and X-ray ORTEP and crystallographic data for com-
pounds 3e and (Ss,Rc)-6a (CIF). This material is available free of
charge via the Internet at http://pubs.acs.org.
(()-(Rc,Ss)-1-(2-Chlorotetrafluorosulfinylamino)-3-methylpentaneni-
trile (6f): white solid; mp 97ꢀ99 °C; FT-IR (KBr) 3185, 2213 cmꢀ1; 1H
NMR (300 MHz, CDCl3) δ (ppm) 5.28 (d, J = 7.2 Hz, 1H), 4.40 (dd,
J = 15.5, 8.3 Hz, 1H), 1.95ꢀ1.84 (m, 2H), 1.80ꢀ1.70 (m, 1H), 1.01 (d, J =
5.7 Hz, 3H), 0.99 (d, J = 4.8 Hz, 3H); 19F NMR (282 MHz, CDCl3) δ
(ppm) ꢀ66.99 (m, 2F), ꢀ114.82 (d, JFF = 230.7 Hz, 1F), ꢀ120.25 (d,
JFF = 230.7 Hz, 1F); 13C NMR (100 MHz, CDCl3) δ (ppm) 121.4 (tt, J =
298.8, 33.2 Hz), 118.4, 116.4 (tt, J = 271.1, 35.9 Hz), 43.2, 42.8, 24.6,
22.1, 21.3; MS (ESI) (M þ NH4)þ 312. Anal. Calcd for C8H11ClF4-
N2OS: C, 32.60; H, 3.76; N, 9.51. Found: C, 32.67; H, 3.76; N, 9.33.
’ AUTHOR INFORMATION
Corresponding Author
*E-mail: jtliu@sioc.ac.cn.
’ ACKNOWLEDGMENT
Financial support from the National Natural Science Founda-
tion of China (No. 20872166) is gratefully acknowledged.
4680
dx.doi.org/10.1021/jo200119x |J. Org. Chem. 2011, 76, 4675–4681

The Journal of Organic Chemistry
NOTE
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