Practical and highly stereoselective method for the preparation of several chiral arylsulfinamides and arylsulfinates based on the spontaneous crystallization of diastereomerically pure N-benzyl-N-(1-phenylethyl)- arylsulfinamides

Article abstract of DOI:10.1016/j.tetasy.2011.01.028

A novel and simple process for the preparation of enantiomerically pure (S_S)-benzenesulfinamide (S_S)-3a, (S_S)-p- toluenesulfinamide (S_S)-3b, (S_S)-p-chloro- benzenesulfinamide (S_S)-3c and (S_S)-p- fluorobenzenesulfinamide (S_S)-3d has been developed. The treatment of arylsulfinyl chlorides with (R)-N-benzyl-1-phenylethanamine in the presence of excess triethylamine gave diastereomeric mixtures of N-benzyl-N-(1-phenylethyl)- arylsulfinamides 1, which underwent spontaneous crystallization to furnish diastereomerically pure (R,S_S)-N-benzyl-N-(1-phenylethyl)- arylsulfinamides (R,S_S)-1a-1d in 28%, 29%, 27% and 31% yields, respectively. The diastereomerically pure compounds (R,S_S)-1 were then converted into four enantiopure (R_S)-methyl arylsulfinates (R_S)-2, and finally into four enantiopure (S_S)- arylsulfinamides (S_S)-3 in good yields.

Full text of DOI:10.1016/j.tetasy.2011.01.028

Tetrahedron: Asymmetry 22 (2011) 387–393
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Practical and highly stereoselective method for the preparation of several chiral
arylsulfinamides and arylsulfinates based on the spontaneous crystallization of
diastereomerically pure N-benzyl-N-(1-phenylethyl)-arylsulfinamides
⇑
Rui-Heng Zhu, Xiao-Xin Shi
Department of Pharmaceutical Engineering, School of Pharmacy, East China University of Science and Technology, PO Box 363, 130 Mei-Long Road, Shanghai 200237, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 20 October 2010
Accepted 7 January 2011
A novel and simple process for the preparation of enantiomerically pure (SS)-benzenesulfinamide (SS)-3a,
(SS)-p-toluenesulfinamide (SS)-3b, (SS)-p-chloro-benzenesulfinamide (SS)-3c and (SS)-p-fluorobenzenesul-
finamide (SS)-3d has been developed. The treatment of arylsulfinyl chlorides with (R)-N-benzyl-1-
phenylethanamine in the presence of excess triethylamine gave diastereomeric mixtures of
N-benzyl-N-(1-phenylethyl)-arylsulfinamides 1, which underwent spontaneous crystallization to furnish
diastereomerically pure (R,SS)-N-benzyl-N-(1-phenylethyl)-arylsulfinamides (R,SS)-1a–1d in 28%, 29%,
27% and 31% yields, respectively. The diastereomerically pure compounds (R,SS)-1 were then converted
into four enantiopure (RS)-methyl arylsulfinates (RS)-2, and finally into four enantiopure (SS)-arylsulfina-
mides (SS)-3 in good yields.
Ó 2011 Elsevier Ltd. All rights reserved.
1. Introduction
2. Results and discussion
Chiral sulfinamides are important compounds in asymmetric
synthesis; they have been extensively utilized as chiral auxiliaries
for the preparation of structurally diverse optically active amines
and amine-derived compounds.1–26 Moreover, enantiopure sulfi-
namides and their derivatives have also been successively used
as chiral ligands in many catalytic asymmetric transforma-
tions.21,27–37
Due to the aforementioned utilities of chiral sulfinamides, the
preparation of these compounds is of considerable interest. A liter-
ature search revealed that enantiopure p-toluenesulfinamide
served as the first widely used auxiliary for asymmetric nucleo-
philic addition of imines,38,39 and that enantiopure tert-butylsulfi-
namide, which was discovered by Ellman et al. in 1997,40 served as
the second versatile auxiliary and was superior to p-toluenesulfi-
namide for some asymmetric processes.1,24,25,40 Although the
synthesis of both enantiopure p-toluenesulfinamide and tert-
butylsulfinamide has been well studied, and hence some elegant
methods for the preparation of these two enantiopure sulfinamides
have been developed,1,38–50 methods for the preparation of other
chiral sulfinamides are relatively rare.48–50 Herein we report our
recent work regarding a novel method for the preparation of sev-
eral chiral arylsulfinamides including (SS)-benzenesulfinamide,
(SS)-p-toluenesulfinamide, (SS)-p-chlorobenzenesulfinamide and
(SS)-p-fluorobenzenesulfinamide.
As depicted in Scheme 1, arylsulfinyl chlorides were prepared
in situ by exposure of arylsulfinic acid sodium salt with oxalyl
chloride in toluene,44 and then the freshly prepared arylsulfinyl
chlorides (R = H, Me, Cl and F) were treated immediately with
(R)-N-benzyl-1-phenylethanamine in the presence of excess trieth-
ylamine to give the corresponding diastereomeric mixtures of N-
benzyl-N-(1-phenylethyl)arylsulfinamides 1a–1d in good yields
but with disappointing stereoselectivities (RRS/RSS = 49:51 for 1a,
51:49 for 1b, 53:47 for 1c and 49:51 for 1d). However, diastereo-
merically pure (de >99%) compounds (R,SS)-1a, (R,SS)-1b, (R,SS)-1c
and (R,SS)-1d could be obtained in 28%, 29%, 27% and 31% respec-
tive yields via spontaneous crystallization in a mixed solvent
(EtOAc/hexane = 1:9), and diastereomerically enriched compounds
1a–1d (RRS/RSS = 75:25 for 1a, 77:23 for 1b, 79:21 for 1c and 76:24
for 1d) being left in the mother liquor. Although the yields of diste-
reomerically pure compounds (R,SS)-1a–1d are relatively low, the
aforementioned spontaneous crystallization process can be easily
scaled up due to the lack of chromatography, meaning that this
method is practical and might be suitable for the preparation of
enantiomerically pure N-benzyl-N-(1-phenylethyl)arylsulfina-
mides (R,SS)-1a–1d in large quantities. Moreover, if necessary,
the diastereomerically enriched compounds 1a–1d in the mother
liquor could be further separated by chromatography to afford an-
other batch of compounds (R,SS)-1a–1d and their diastereomers
(R,RS)-1a–1d. It is worthy of note that use of (R)-N-benzyl-1-phen-
ylethanamine was crucial for the spontaneous crystallization, be-
cause when other chiral amines such as (R)-1-phenylethanamine
⇑
Corresponding author.
E-mail address: xxshi@ecust.edu.cn (X.-X. Shi).
0957-4166/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2011.01.028

388
R.-H. Zhu, X.-X. Shi / Tetrahedron: Asymmetry 22 (2011) 387–393
O
S
O
S
O
S
N
ONa
a
Cl
1a (R = H), 81%
1b (R = Me), 85%
1c (R = Cl), 82%
1d (R = F), 87%
b
R
R
R
c
O
S
O
S
N
N
R
R
(Spontaneous crystallization)
(Mother liquior)
1a (R,RS/R,SS = 75:25), 53%
1b (R,RS/R,SS = 77:23), 56%
1c (R,RS/R,SS = 79:21), 55%
1d (R,RS/R,SS = 76:24), 56%
(R,SS)-1a, 28%
(R,SS)-1b, 29%
(R,SS)-1c, 27%
(R,SS)-1d, 31%
Scheme 1. Preparation of (R,SS)-N-benzyl-N-(1-phenylethyl)arylsulfinamides (R,SS)-1 via spontaneous crystallization. Reagents and conditions: (a) Oxalyl chloride (1.05
equiv), 0 °C for 1 h, and then rt for 2 h in toluene. (b) Et3N (2 equiv), (R)-N-benzyl-1-phenylethanamine (1.2 equiv), 0 °C to rt for 2 h in toluene. (c) Stirring at rt for 2 h in a
mixed solvent (EtOAc/Hexane = 1:9), and then standing at rt overnight.
or (R)-N-allyl-1-phenylethanamine or (R)-N-methyl-1-phenyl-eth-
anamine were used instead of (R)-N-benzyl-1-phenylethanamine
for the reaction, no spontaneous crystallization occurred at all.
The absolute configurations of the chiral sulfur atoms of the
aforementioned four diastereomerically pure N-benzyl-N-(1-phen-
ylethyl)-arylsulfinamides (R,SS)-1a–1d were assigned either by
converting them into authentic sulfoxides or by cultivating their
single crystals for X-ray analysis. When compounds (R,SS)-1a and
(R,SS)-1b were exposed to butyllithium at ꢀ78 °C in tetrahydrofu-
ran,51 (SS)-butylphenylsulfoxide52 and (SS)-butyl-p-tolylsulfoxide53
were obtained in 75% and 78% yields, respectively, meaning that
both arylsulfinamides (R,SS)-1a and (R,SS)-1b have an (SS)-absolute
configuration at the sulfur atom, indicating a Waldern type inver-
sion and a change of preferential sequence of substituents during
the conversions of sulfinamides (R,SS)-1a and (R,SS)-1b into sulfox-
ides. For the other two diastereomerically pure compounds (R,SS)-
1c and (R,SS)-1d, the absolute configurations of the sulfur atoms
were determined unequivocally by X-ray diffraction analysis of
the corresponding single crystals; the ORTEP drawing of the com-
pounds (R,SS)-1c and (R,SS)-1d are shown in Figures 1 and 2,
respectively.
Figure 1. ORTEP drawing of (R,SS)-N-benzyl-N-(1-phenylethyl)-p-chlorobenzene-
sulfinamide (R,SS)-1c.
The four diastereomerically pure N-benzyl-N-(1-phenylethyl)-
arylsulfinamides (R,SS)-1a–1d could be used as productive inter-
mediates for chiral arylsulfinates and arylsulfinamides. As shown
in Scheme 2, we first attempted to convert them into enantiopure
(RS)-methyl benzenesulfinate (RS)-2a,54 (RS)-methyl p-toluenesulf-
inate (RS)-2b,55 (RS)-methyl p-chlorobenzenesulfinate (RS)-2c and
(RS)-methyl p-fluorobenzenesulfinate (RS)-2d. Lewis acid-catalyzed
transformation of N-benzyl-N-(1-phenylethyl)arylsulfinamides
(R,SS)-1 into methyl arylsulfinates (RS)-2 under various conditions
was investigated fully, and the results are summarized in Table 1.
Although high yields were obtained under all circumstances
(Table 1, entries 1–20), partial racemization in some instances oc-
curred at the sulfur atom probably due to the transesterification of
the sulfinates under the acidic conditions.56,57 Toluene was found
to be the best solvent, when arylsulfinamides (R,SS)-1 were treated
with 3 equiv of methanol and 1.5 equiv of BF3ꢁOEt2 at ꢀ5 °C in tol-
uene, arylsulfinates (RS)-2 could be obtained in nearly quantitative
yields without observable racemization (entries 6, 15, 19 and 20).
An increase of the amount of methanol favored the transesterifica-
tion of sulfinates, and thus tended to facilitate racemization
(entries 1, 7 and 8). A lower temperature was crucial for the
reaction, since when the conversion was performed at room tem-
perature (20 °C), racemization would take place rapidly (entries
11 and 18).
Finally, enantiopure sulfinamides (SS)-3a,58 (SS)-3b,59 (SS)-3c48
and (SS)-3d were prepared from enantiopure sulfinates (RS)-2a,
(RS)-2b, (RS)-2c and (RS)-2d, respectively. Normally, sulfinates can
be converted into sulfinamides by treating them either with LiNH2
in liquid ammonia49 or with LiN(SiMe3)2 in THF.42 Herein, enantio-
pure sulfinates (RS)-2a–2d were treated first with LiN(SiMe3)2 and
then with aqueous NH4Cl in an one-pot procedure to afford enan-
tiopure sulfinamides (SS)-3a–3d in good yields, the (RS)-configura-
tion of the sulfur atoms changed into the (SS)-configuration via a
Waldern type inversion during the conversion.
We also attempted to prepare enantiopure sulfinamides (SS)-
3a–3d from diastereomerically pure N-benzyl-N-(1-phenyl-
ethyl)arylsulfinamides (R,SS)-1a–1d via direct reductive removal
of the benzyl groups (see also Scheme 2). However, when Pd/C, P-2
nickel,60 Raney-Ni or PtO2 was used as the catalyst, hydrogenation

R.-H. Zhu, X.-X. Shi / Tetrahedron: Asymmetry 22 (2011) 387–393
389
the highly stereoselective, spontaneous, crystallization of com-
pounds (R,SS)-1a–1d from diastereomeric mixtures of N-benzyl-
N-(1-phenylethyl)-arylsulfinamides 1a–1d. No chromatography
and the easy operation over the whole process allow us to easily
synthesize enantiopure arylsulfinamides (SS)-3a–3d in gram quan-
tities despite low overall yields. Moreover, four enantiomerically
pure arylsulfinates (RS)-2a–2d were also obtained in the synthesis,
which may be useful chiral intermediates for the synthesis of chiral
sulfoxides.61,62
In addition, it should be pointed out that when we started with
(S)-N-benzyl-1-phenylethanamine instead of (R)-N-benzyl-1-
phenylethanamine, we could accordingly obtain four enantiopure
arylsulfinamides (RS)-3a–3d as well as four enantiopure arylsulfi-
nates (SS)-2a–2d by the same method described in this paper.
4. Experimental
4.1. General methods
Melting points are uncorrected. 1H NMR and 13C NMR spectra
were acquired on Bruker AM-500. Chemical shifts are given on
the delta scale as parts per million (ppm) with tetramethylsilane
(TMS) as the internal standard. IR spectra were recorded on Nicolet
Magna IR-550. Mass spectra were recorded on HP5989A. Optical
rotations of chiral compounds were measured on WZZ-1S auto-
matic polarimeter at room temperature. HPLC analysis was per-
formed with an Agilent/HP 1100 series equipped with an Alltech
ELSD 2000ES detector. All chemicals were analytically pure and
used as such from commercial suppliers.
Figure 2. ORTEP drawing of (R,SS)-N-benzyl-N-(1-phenylethyl)-p-flurobenzenesul-
finamide (R,SS)-1d.
O
S
O
S
N
a
OMe
R
R
(RS)-2a (R = H), 99%
(RS)-2b (R = Me), 99%
(RS)-2c (R = Cl), 98%
(RS)-2d (R = F), 98 %
(R,SS)-1a (R = H)
(R,SS)-1b (R = Me)
(R,SS)-1c (R = Cl)
(R,SS)-1d (R = F)
4.2. (R)-N-Benzyl-1-phenylethanamine
To a solution of (R)-(+)-1-phenylethanamine (48.47 g, 0.40 mol)
in toluene (300 mL), was added benzaldehyde (43.51 g, 0.41 mol).
The resulting solution was heated at reflux. Stirring was then con-
tinued at reflux for around 3 h and water was removed by azeotro-
pic distillation with a Dean–Stark trap during refluxing. After the
reaction was complete, the solvent was removed by vacuum distil-
lation to give a residue as pale yellow oil, which was then dissolved
in anhydrous methanol (300 mL). The solution was cooled down to
0 °C with an ice bath, and the powdered NaBH4 (15.52 g, 0.41 mol)
was added in portions over 0.5 h. After the addition was complete,
the mixture was stirred at 0 °C for a further 2 h, and the reaction
was traced by TLC (EtOAc/hexane = 1:6). When the reaction was
complete, methanol was removed by vacuum distillation. The solid
residue was then partitioned between toluene (300 mL) and water
(150 mL). Two phases were separated, and the aqueous phase was
extracted twice with toluene (2 ꢂ 75 mL). The extracts were com-
bined and dried over anhydrous MgSO4. Evaporation of toluene un-
der vacuum gave an oily residue, which was dissolved in ethanol
(250 mL). Concentrated hydrochloric acid (40 mL, 12 M, 0.48 mol)
was added, and the mixture was heated at reflux for 2 h. After
the solution was concentrated to dryness, a residue was obtained
as a pale yellow solid. A mixed solvent of ethyl acetate (100 mL)
and hexane (200 mL) was added. The suspension was stirred at re-
flux for 2 h. After the suspension was cooled to room temperature,
the off-white solid was collected on Buchner funnel by suction, and
was rinsed with a mixed solvent (EtOAc/hexane = 1:3). The solid
was then partitioned between ethyl acetate (400 mL) and aqueous
sodium hydroxide (250 mL, 20% w/v). Two phases were separated
and the aqueous phase was extracted twice with ethyl acetate
(2 ꢂ 100 mL). After the combined extracts were dried over anhy-
drous MgSO4, evaporation of the solvent under vacuum afforded
(R)-N-benzyl-1-phenylethanamine (78.1 g, 0.37 mol) as colorless
b
Direct reductive removal
of benzyl groups
O
S
NH2
R
(SS)-3a (R = H), 84%
(SS)-3b (R = Me), 86%
(SS)-3c (R = Cl), 83%
(SS)-3d (R = F), 88%
Scheme 2. Preparation of enantiopure (RS)-arylsulfinates (RS)-2 and (SS)-arylsulfin-
amides (SS)-3 from diastereomerically pure compounds (R,SS)-1. Reagents and
conditions: (a) BF3ꢁOEt2 (1.5 equiv), CH3OH (3 equiv), ꢀ5 °C for 2.5 h in toluene. (b)
LIN(SiMe3)2 (1.5 equiv), ꢀ78 °C for 3 h in THF; and then aqueous NH4Cl, ꢀ78 °C to rt
for 2 h.
of N-benzyl-N-(1-phenylethyl)arylsulfinamides (R,SS)-1a–1d in
various solvents at different temperatures failed to give desired
sulfinamides (SS)-3a–3d. The hydrogenation of all four sulfina-
mides (R,SS)-1a–1d was sluggish at room temperature, and gave
a complex mixture after prolonged heating.
3. Conclusion
In conclusion,
a novel, simple, highly stereoselective and
practical method for the preparation of enantiomerically pure
(SS)-arylsulfinamides (SS)-3a–3d is described. Enantiopure (SS)-
benzenesulfinamide (SS)-3a, (SS)-p-toluenesulfinamide (SS)-3b,
(SS)-p-chlorobenzenesulfinamide (SS)-3c and (SS)-p-fluorobenzene-
sulfinamide (SS)-3d were synthesized from the corresponding aryl-
sulfinic acids sodium salts via four steps in 23.3%, 24.7%, 22.0% and
26.7% overall yields, respectively. The key point of the method was
oil in 92% yield. ½a D25
ꢃ
¼ þ59:1 (c 1.2, EtOH) {lit.63
½
a 2D5
ꢃ
¼ þ56:2 (c
1.1, EtOH)}. 1H NMR (CDCl3) d 1.40 (d, J = 6.6 Hz, 3H), 3.63 (d,

390
R.-H. Zhu, X.-X. Shi / Tetrahedron: Asymmetry 22 (2011) 387–393
Table 1
Conversion of diastereomerically pure N,N-disubstituted arylsulfinamides (R,SS)-1 into chiral methyl arylsulfinates (RS)-2 under various conditions
½ ꢃ
a 2D5
Entry
(R,SS)-1
Solvent
CH3OH (equiv)
BF3ꢁOEt2 (equiv)
T (°C)
t (h)
(RS)-2
Eea (%)
Yieldb (%)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1b
1b
1b
1b
1b
1c
1d
CH3OH
THF
CH2Cl2
—
3
3
3
2
3
5
10
3
3
3
3
3
3
3
3
3
3
3
3
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
2
ꢀ5
ꢀ5
ꢀ5
ꢀ5
ꢀ5
ꢀ5
ꢀ5
ꢀ5
0
1
6
2.5
5
4
2.5
2
1.5
2
1.5
1
2
1.5
4
2.5
2
1.5
1
2.5
2.5
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2b
2b
2b
2b
2b
2c
2d
ꢀ148.5
ꢀ167.4
ꢀ189.2
ꢀ175.0
ꢀ194.1
ꢀ195.0c
ꢀ189.5
ꢀ181.1
ꢀ193.1
ꢀ179.2
ꢀ156.9
ꢀ193.5
ꢀ190.1
ꢀ210.2
ꢀ210.2d
ꢀ209.0
ꢀ194.4
ꢀ170.3
ꢀ173.0e
ꢀ171.9f
76
86
97
90
88
95
91
96
99
98
97
97
97
94
98
97
95
99
98
96
93
98
98
CHCl3
90
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
>98
>98
97
93
98
10
20
92
80
ꢀ5
ꢀ5
ꢀ11
ꢀ5
0
>98
97
>98
>98
98
93
81
>98
>98
3
1.5
1.5
1.5
1.5
1.5
1.5
1.5
10
20
ꢀ5
ꢀ5
a
b
c
d
e
f
Ee values were estimated according to high-resolution 1H NMR (500 MHz) using (S)-2,2,2-trifluoro-1-phenylethanol as the chiral shift reagent.55
Isolated yield.
For enantiopure compound (RS)-2a: ½a D25
ꢃ
¼ ꢀ195:0 (c 1.2, EtOH) {lit.54
[a]589 = ꢀ188.0 (c 1.5, EtOH)}.
For enantiopure compound (RS)-2b: ½a D25
ꢃ
¼ ꢀ210:2 (c 1.4, EtOH) {lit. ½a D25
ꢃ
¼ ꢀ211:7 (c 4.5, EtOH), calculated from the data of ½a D25
ꢃ
¼ ꢀ25:4 (c 4.5, EtOH, 12% ee) in Ref. 55}.
For enantiopure compound (RS)-2c: ½a D25
ꢃ
¼ ꢀ173:0 (c 1.3, EtOH).
¼ ꢀ171:9 (c 1.3, EtOH).
For enantiopure compound (RS)-2d: ½a D25
ꢃ
J = 13.1 Hz, 1H), 3.69 (d, J = 13.1 Hz, 1H), 3.84 (q, J = 6.6 Hz, 1H),
7.24–7.40 (m, 10H). MS m/z (%) 212 (M++1, 100), 196 (56), 91 (48).
J = 15.2 Hz, 1H), 4.07 (d, J = 15.2 Hz, 1H), 4.47 (q, J = 7.2 Hz, 1H),
7.01 (dd, J1 = 7.8 Hz, J2 = 1.8 Hz, 2H), 7.15–7.24 (m, 3H), 7.29 (t,
J = 7.3 Hz, 1H), 7.37 (t, J = 7.7 Hz, 2H), 7.47–7.54 (m, 3H), 7.55–
7.61 (m, 2H), 7.82 (dd, J1 = 7.1 Hz, J2 = 1.4 Hz, 2H). 13C NMR (ace-
tone-d6) d 22.1, 48.3, 59.3, 127.3, 128.4, 128.6, 129.2, 129.4,
129.5, 129.6, 130.1, 132.0, 138.6, 142.2, 146.4. MS m/z (%) 335
(M+, 2), 320 (3), 258 (1), 231 (3), 210 (85), 194 (16), 167 (3), 140
(4), 125 (17), 105 (100), 91 (82), 77 (16), 65 (7). IR (KBr film)
3063, 3021, 2979, 2926, 2905, 1600, 1584, 1495, 1453, 1436,
1084, 1053, 911, 868, 768, 753, 737, 700, 537, 500, 463 cmꢀ1. Anal.
Calcd for C21H21NOS: C, 75.19; H, 6.31; N, 4.18. Found: C, 75.38; H,
6.17; N, 4.14.
4.3. Typical procedure for the preparation of (R,SS)-N-benzyl-N-
(1-phenylethyl)-arylsulfinamides (R,SS)-1
To a suspension of benzenesulfinic acid sodium salt (16.42 g,
0.10 mol) in toluene (150 mL), was dropwise added oxalyl chloride
(13.33 g, 0.105 mol) over 10 min at 0 °C. After the addition was fin-
ished, stirring was continued at 0 °C for one more hour and at room
temperature for 2 h. The mixture obtained was then added into a
cooled solution of (R)-N-benzyl-1-phenylethanamine (25.36 g,
0.12 mol) and triethylamine (20.3 g, 0.20 mol) in toluene (50 mL)
over 15 min at 0 °C. After the addition was finished, the ice bath
was removed, and the mixture was stirred further for around 2 h,
while the temperature was allowed to gradually rise to room tem-
perature. An aqueous solution of citric acid (150 mL, 15% w/v) was
added, and the mixture was vigorously stirred for 5 min. Two
phases were separated, and the aqueous phase was extracted twice
with toluene (2 ꢂ 50 mL). The extracts were combined, and
washed successively with saturated aqueous solution of NaHCO3
(30 mL) and brine (20 mL). After the organic solution was dried
over anhydrous Na2SO4, the solvent was removed by vacuum dis-
tillation to give a residue. A mixed solvent of ethyl acetate (20 mL)
and hexane (180 mL) was added, the mixture was stirred at room
temperature for 2 h, and then was allowed to stand at room tem-
perature overnight. Finally, filtration by suction through a Buchner
funnel afforded (R,SS)-N-benzyl-N-(1-phenylethyl)benzenesulfina-
mide (R,SS)-1a (9.40 g, 28.02 mmol) in 28% yield. The mother liquid
was then concentrated under vacuum to give a residue, which was
purified by chromatography (eluent: EtOAc/hexane = 1:16) to give
second batch of compound (R,SS)-1a (4.45 g, 13.26 mmol) in 13%
yield and its diastereomer (R,RS)-1a (13.33 g, 39.74 mmol) in 40%
yield.
4.3.2. (R,RS)-N-Benzyl-N-(1-phenylethyl)benzenesulfinamide
(R,RS)-1a
Pale yellow oil, Rf = 0.50 (EtOAc/hexane = 1:4), ½a D25
¼ þ111:1 (c
ꢃ
4.1, EtOAc). 1H NMR (acetone-d6) d 1.74 (d, J = 7.0 Hz, 3H), 3.98 (d,
J = 14.8 Hz, 1H), 4.05 (d, J = 14.8 Hz, 1H), 4.44 (q, J = 7.0 Hz, 1H),
7.16 (dd, J1 = 8.0 Hz, J2 = 1.5 Hz, 2H), 7.20–7.37 (m, 8H), 7.47–7.58
(m, 3H), 7.63 (dd, J1 = 8.1 Hz, J2 = 1.3 Hz, 2H). 13C NMR (CDCl3) d
18.3, 47.9, 57.1, 126.2, 127.5, 127.6, 127.8, 128.4, 128.5, 128.9,
129.1, 130.8, 137.2, 141.8, 144.4. MS m/z (%) 335 (M+, 2), 320 (4),
258 (1), 231 (4), 210 (86), 194 (18), 167(3), 140 (4), 125 (18),
105 (100), 91 (75), 77 (8), 65 (5). HRMS (EI) m/z calcd for
C
21H21NOS [M]+: 335.1344, found 335.1350. IR (neat) 3063, 3021,
2979, 2937, 1600, 1584, 1495, 1453, 1379, 1358, 1205, 1089,
1058, 1026, 911, 868, 753, 700, 537, 505, 474 cmꢀ1
.
4.3.3. (R,SS)-N-Benzyl-N-(1-phenylethyl)-p-toluenesulfinamide
(R,SS)-1b
Rf = 0.62 (EtOAc/hexane = 1:4), mp 125–126 °C, ½a D25
¼ þ32:1 (c
ꢃ
1.2, EtOAc). 1H NMR (acetone-d6) d 1.55 (d, J = 7.2 Hz, 3H), 2.38 (s,
3H), 3.69 (d, J = 15.2 Hz, 1H), 4.05 (d, J = 15.2 Hz, 1H), 4.46 (q,
J = 7.2 Hz, 1H), 7.02 (dd, J1 = 7.9 Hz, J2 = 1.9 Hz, 2H), 7.16–7.24 (m,
3H), 7.25–7.31 (m, 1H), 7.32–7.40 (m, 4H), 7.50 (dd, J1 = 8.2 Hz,
J2 = 1.2 Hz, 2H), 7.69 (d, J = 8.2 Hz, 2H). 13C NMR (acetone-d6) d
21.6, 22.1, 48.3, 59.3, 127.4, 128.3, 128.6, 129.2, 129.4, 129.5,
129.6, 130.7, 138.7, 142.3, 142.4, 143.3. MS m/z (%) 349 (M+, 3),
334 (4), 245 (3), 210 (100), 194 (10), 154 (7), 139 (29), 105 (50),
4.3.1. (R,SS)-N-Benzyl-N-(1-phenylethyl)benzenesulfinamide
(R,SS)-1a
Rf = 0.60 (EtOAc/hexane = 1:4), mp 110–111 °C, ½a D25
¼ þ42:2 (c
ꢃ
1.1, EtOAc). 1H NMR (acetone-d6) d 1.56 (d, J = 7.2 Hz, 3H), 3.70 (d,

R.-H. Zhu, X.-X. Shi / Tetrahedron: Asymmetry 22 (2011) 387–393
391
91 (42), 77 (6), 65 (4). IR (KBr film) 3032, 2916, 1595, 1489, 1453,
1084, 911, 868, 821, 763, 732, 700, 647, 537, 505, 453 cmꢀ1. Anal.
Calcd for C22H23NOS: C, 75.61; H, 6.63; N, 4.01. Found: C, 75.83; H,
6.46; N, 3.98.
J = 14.7 Hz, 1H), 3.96 (d, J = 14.7 Hz, 1H), 4.33 (q, J = 7.0 Hz, 1H),
7.00 (dd, J1 = 7.9 Hz, J2 = 1.5 Hz, 2H), 7.06 (t, J = 8.6 Hz, 2H), 7.12–
7.22 (m, 6H), 7.25 (dd, J1 = 6.9 Hz, J2 = 7.7 Hz, 2H), 7.42–7.49 (m,
2H). 13C NMR (CDCl3) d 18.3, 47.8, 57.2, 115.9, 116.1, 127.6,
127.7, 127.8, 128.4, 128.49, 128.52, 129.0, 137.0, 139.94, 139.97,
141.7, 163.0, 165.5. HRMS (EI) m/z calcd for C21H20FNOS [M]+:
353.1250, found 353.1252. IR (neat) 3063, 3030, 2974, 1587,
4.3.4. (R,RS)-N-Benzyl-N-(1-phenylethyl)-p-toluenesulfinamide
(R,RS)-1b
Pale yellow oil, Rf = 0.50 (EtOAc/hexane = 1:4), ½a D25
ꢃ
¼ þ128:7 (c
1487, 1454, 1223, 1151, 1065, 1027, 837, 814, 751, 699 cmꢀ1
.
4.4, EtOAc). 1H NMR (acetone-d6) d 1.73 (d, J = 7.0 Hz, 3H), 2.35 (s,
3H), 3.96 (d, J = 14.8 Hz, 1H), 4.05 (d, J = 14.8 Hz, 1H), 4.42 (q,
J = 7.0 Hz, 1H), 7.18 (dd, J1 = 8.1 Hz, J2 = 1.6 Hz, 2H), 7.21–7.37 (m,
10H), 7.52 (d, J = 8.2 Hz, 2H). 13C NMR (CDCl3) d 18.3, 21.4, 47.8,
57.0, 126.2, 127.4, 127.5, 127.8, 128.38, 128.42, 129.1, 129.6,
137.3, 141.1, 141.2, 141.9. HRMS (EI) m/z calcd for C22H23NOS
[M]+: 349.1500, found 349.1499. IR (neat) 3021, 2979, 2916,
1600, 1495, 1453, 1379, 1089, 1063, 911, 868, 816, 753, 700,
4.4. Typical procedure for the preparation of (RS)-methyl
arylsulfinates (RS)-2
Compound (R,SS)-1a (3.35 g, 9.99 mmol) was dissolved in tolu-
ene (20 mL), after which methanol (0.96 g, 29.96 mmol) was
added, and the mixture was cooled to ꢀ5 °C with a salt-ice bath.
A solution of BF3ꢁOEt2 (2.13 g, 15.01 mmol) in toluene (10 mL)
was added dropwise over 5 min, and the mixture was stirred at
ꢀ5 °C for around 2.5 h. The reaction was monitored by TLC
(EtOAc/hexane = 1:6). After the mixture was diluted with toluene
(50 mL), the reaction was quenched by adding an aqueous satu-
rated solution of NaHCO3 (20 mL). The organic phase was sepa-
rated, and then washed successively with an aqueous solution of
citric acid (20 mL, 15% w/v) and aqueous saturated solution of
NaHCO3 (5 mL). The organic solution was dried over anhydrous
MgSO4. The solvent was removed by vacuum distillation to afford
(RS)-methyl benzenesulfinate (RS)-2a (1.54 g, 9.86 mmol) as a col-
orless oil in 99% yield. All aqueous phases were combined and ad-
justed to pH P 10 by adding powdered KOH. The resulting
aqueous mixture was then twice extracted with ethyl acetate
(2 ꢂ 50 mL). The organic extracts were combined and dried over
anhydrous MgSO4. Removal of the solvent by vacuum distillation
gave a pale yellow oily residue. After flash chromatography
through a short column (5–8 cm) of silica gel, pure (R)-N-benzyl-
1-phenylethanamine (2.07 g, 9.80 mmol) was recovered in 98%
yield and could be re-used in the preparation of compounds 1.
505 cmꢀ1
.
4.3.5. (R,SS)-N-Benzyl-N-(1-phenylethyl)-p-chlorobenzenesulfin-
amide (R,SS)-1c
Rf = 0.55 (EtOAc/hexane = 1:4), mp 155–156 °C, ½a D25
¼ þ22:7 (c
ꢃ
1.2, EtOAc). 1H NMR (CDCl3) d 1.60 (d, J = 7.1 Hz, 3H), 3.73 (d,
J = 15.1 Hz, 1H), 4.05 (d, J = 15.1 Hz, 1H), 4.45 (q, J = 7.1 Hz, 1H),
6.92 (dd, J1 = 7.1 Hz, J2 = 2.2 Hz, 2H), 7.17–7.25 (m, 3H), 7.31 (t,
J = 7.2 Hz, 1H), 7.39 (t, J = 7.6 Hz, 2H), 7.45 (d, J = 7.9 Hz, 2H), 7.47
(d, J = 8.5 Hz, 2H), 7.69 (d, J = 8.4 Hz, 2H). 13C NMR (CDCl3) d 21.6,
47.5, 58.8, 127.4, 127.8, 127.9, 128.0, 128.4, 128.5, 128.7, 129.1,
137.0, 137.1, 140.5, 143.3. MS m/z (%) 369 (M+, 1), 354 (3), 265
(2), 210 (62), 194 (10), 159 (26), 105 (100), 91 (69), 77 (13), 65
(7). HRMS (EI) m/z calcd for C21H20ClNOS [M]+: 369.0954, found
369.0946. IR (KBr film) 3086, 3029, 2943, 1494, 1470, 1453,
1379, 1103, 1076, 1066, 1051, 1009, 868, 767, 742, 702, 538 cmꢀ1
.
4.3.6. (R,RS)-N-Benzyl-N-(1-phenylethyl)-p-chlorobenzenesulfin-
amide (R,RS)-1c
Rf = 0.45 (EtOAc/hexane = 1:4), mp 80–81 °C, ½a D25
¼ þ137:4 (c
ꢃ
2.3, EtOAc). 1H NMR (CDCl3) d 1.78 (d, J = 7.0 Hz, 3H), 3.97 (d,
J = 14.7 Hz, 1H), 4.05 (d, J = 14.7 Hz, 1H), 4.41 (q, J = 7.0 Hz, 1H),
7.10 (d, J = 7.0 Hz, 2H), 7.22–7.30 (m, 6H), 7.34 (dd, J1 = 7.2 Hz,
J2 = 7.6 Hz, 2H), 7.43 (d, J = 8.5 Hz, 2H), 7.49 (d, J = 8.5 Hz, 2H). 13C
NMR (CDCl3) d 18.3, 48.0, 57.3, 127.6, 127.72, 127.74, 127.8,
128.5, 128.6, 129.0, 129.1, 136.9, 137.1, 141.7, 143.0. HRMS (EI)
m/z calcd for C21H20ClNOS [M]+: 369.0954, found 369.0948. IR
(KBr film) 3084, 3028, 2914, 1574, 1494, 1469, 1455, 1375, 1203,
1128, 1102, 1080, 1066, 1008, 984, 913, 856, 831, 765, 743,
4.4.1. (RS)-Methyl benzenesulfinate (RS)-2a
½
a 2D5
ꢃ
¼ ꢀ195:0 (c 1.2, EtOH) {lit.54
½
a 2D5
ꢃ
¼ ꢀ188:0 (c 1.5, EtOH)}.
1H NMR (CDCl3) d 3.48 (s, 3H), 7.52–7.59 (m, 3H), 7.68–7.74 (m,
2H). MS m/z (%) 156 (M+, 3), 141 (63), 125 (38), 77 (100), 65 (6),
51 (20). IR (neat) 3063, 2985, 2955, 1762, 1582, 1475, 1446,
1363, 1327, 1188, 1145, 1078, 999, 883, 788, 753, 715, 687, 595,
539, 503, 461 cmꢀ1
.
4.4.2. (RS)-Methyl p-toluenesulfinate (RS)-2b
698 cmꢀ1
.
½
a 2D5
ꢃ
¼ ꢀ210:2 (c 1.4, EtOH) {lit. ½a D25
¼ ꢀ211:7 (c 4.5, EtOH),
ꢃ
calculated from the data of ½a D25
¼ ꢀ25:4 (c 4.5, EtOH, 12% ee) in
ꢃ
4.3.7. (R,SS)-N-Benzyl-N-(1-phenylethyl)-p-fluorobenzenesulfin-
amide (R,SS)-1d
Ref. 55}. 1H NMR (CDCl3) d 2.43 (s, 3H), 3.47 (s, 3H), 7.35 (d,
J = 8.0 Hz, 2H), 7.59 (d, J = 8.0 Hz, 2H). MS m/z (%) 170 (M+, 52),
155 (1), 139 (100), 124 (2), 111 (6), 107 (5), 91 (24), 77 (9), 65
(12). IR (neat) 2940, 1916, 1761, 1596, 1453, 1134, 1082, 964,
Rf = 0.52 (EtOAc/hexane = 1:4), mp 161–162 °C, ½a D25
¼ þ39:7 (c
ꢃ
1.0, EtOAc). 1H NMR (CDCl3) d 1.60 (d, J = 7.2 Hz, 3H), 3.71 (d,
J = 15.1 Hz, 1H), 4.07 (d, J = 15.1 Hz, 1H), 4.45 (q, J = 7.2 Hz, 1H),
6.88–6.94 (m, 2H), 7.15–7.22 (m, 5H), 7.27–7.33 (m, 1H), 7.38
(dd, J1 = 7.2 Hz, J2 = 7.7 Hz, 2H), 7.45 (dd, J1 = 7.2 Hz, J2 = 1.5 Hz,
2H), 7.71–7.79 (m, 2H). 13C NMR (CDCl3) d 21.6, 47.3, 58.7, 115.9,
116.1, 127.4, 127.8, 128.0, 128.4, 128.5, 128.6, 128.7, 137.2,
140.28, 140.31, 140.6, 163.0, 165.5. MS m/z (%) 353 (M+, 1), 338
(4), 249 (4), 210 (83), 194 (12), 143 (17), 105 (100), 91 (54), 77
(7), 65 (4). HRMS (EI) m/z calcd for C21H20FNOS [M]+: 353.1250,
found 353.1256. IR (KBr film) 3087, 3066, 3030, 2922, 1585,
814, 713, 682, 628, 574, 447 cmꢀ1
.
4.4.3. (RS)-Methyl p-chlorobenzenesulfinate (RS)-2c
½
a 2D5
ꢃ
¼ ꢀ173:0 (c 1.3, EtOH). 1H NMR (CDCl3) d 3.49 (s, 3H), 7.53
(d, J = 8.5 Hz, 2H), 7.66 (d, J = 8.5 Hz, 2H). 13C NMR (CDCl3) d 49.7,
126.9, 129.4, 138.6, 142.5. HRMS (ESI) m/z calcd for C7H8ClO2S
[M+H]+: 190.9934, found 190.9922. IR (neat) 3085, 2941, 1915,
1574, 1475, 1391, 1135, 1087, 961, 826, 744, 711, 687, 592, 577,
504, 485, 429 cmꢀ1
.
1493, 1454, 1219, 1084, 1065, 870, 768, 697 cmꢀ1
.
4.4.4. (RS)-Methyl p-fluorobenzenesulfinate (RS)-2d
4.3.8. (R,RS)-N-Benzyl-N-(1-phenylethyl)-p-fluorobenzenesulfin-
amide (R,RS)-1d
½
a 2D5
ꢃ
¼ ꢀ171:9 (c 1.3, EtOH). 1H NMR (CDCl3) d 3.49 (s, 3H),
7.20–7.30 (m, 2H), 7.66–7.76 (m, 2H). 13C NMR (CDCl3) d 49.6,
Pale yellow oil, Rf = 0.41 (EtOAc/hexane = 1:4), ½a D25
¼ þ105:8 (c
ꢃ
1.2, EtOAc). 1H NMR (CDCl3) d 1.69 (d, J = 7.0 Hz, 3H), 3.90 (d,
116.2, 116.4, 127.8, 127.9, 139.76, 139.79, 163.7, 166.3. HRMS

392
R.-H. Zhu, X.-X. Shi / Tetrahedron: Asymmetry 22 (2011) 387–393
(EI) m/z calcd for C7H7FO2S [M]+: 174.0151, found 174.0148. IR
for (SS), 0.42% for (SR). 1H NMR (CDCl3) d 4.46 (s, 2H), 7.07–7.15
(m, 2H), 7.61–7.69 (m, 2H). 13C NMR (DMSO-d6) d 115.5, 115.7,
127.9, 128.0, 144.10, 144.13, 162.0, 164.5. HRMS (EI) m/z calcd
for C6H6NOSF [M]+: 159.0154, found 159.0153. IR (KBr film)
3278, 3164, 3072, 1591, 1491, 1398, 1241, 1158, 1090, 1022,
(neat) 3070, 2943, 1907, 1724, 1590, 1492, 1230, 1132, 1093,
963, 838, 717, 685, 573, 452 cmꢀ1
.
4.5. Typical procedure for the preparation of (SS)-
arylsulfinamides (SS)-3
1011, 837, 816, 672, 533, 436 cmꢀ1
.
A solution of compound (RS)-2a (1.35 g, 8.64 mmol) in anhy-
drous THF (20 mL) was cooled to ꢀ78 °C by a dry-ice bath under
an atmosphere of argon. A solution of LiN(SiMe3)2 in toluene
(13 mL, 1 M, 13.00 mmol) was injected via a syringe. The mixture
was stirred at ꢀ78 °C for around 3 h, and the reaction was moni-
tored by TLC (EtOAc/hexane = 1:3). After the reaction was com-
plete, an aqueous saturated solution of NH4Cl (20 mL) was added,
and the dry-ice bath was removed. Stirring was continued for
2 h, while the temperature was allowed to gradually to rise to
room temperature. Ethyl acetate (20 mL) and water (20 mL) were
added. The two phases were separated, and aqueous phase was ex-
tracted twice with ethyl acetate (2 ꢂ 20 mL). The extracts were
combined, and washed successively with an aqueous saturated
solution of NaHCO3 (10 mL) and brine (10 mL). After the organic
solution was dried over anhydrous MgSO4, solvent was then re-
moved by vacuum distillation. The crude solid product was then
triturated in a mixed solvent of ether and hexane (1:1). (SS)-ben-
zenesulfinamide (RS)-3a (1.03 g, 7.29 mmol) was obtained as white
crystal in 84% yield after suction.
4.6. Determination of the absolute configurations of (R,SS)-N-
benzyl-N-(1-phenylethyl)-arylsulfinamides (R,SS)-1a–1d
4.6.1. Conversion of compounds (R,SS)-1a and (R,SS)-1b into (SS)-
butylphenylsulfoxide and (SS)-butyl-p-tolylsulfoxide to
determine their absolute configurations
A solution of compound (R,SS)-1a (336 mg, 1.00 mmol) in anhy-
drous THF (5 mL) was cooled to ꢀ78 °C by a dry-ice bath under an
atmosphere of argon. A solution of n-BuLi (1.5 mL, 1 M, 1.50 mmol)
in THF was injected via syringe, and the mixture was then stirred at
ꢀ78 to ꢀ50 °C for 4 h. After the reaction was complete as shown by
TLC (EtOAc/hexane = 1:3), it was quenched by adding a dilute
aqueous solution of HCl (2 M, 10 mL). The mixture was extracted
twice with ethyl acetate (2 ꢂ 20 mL). Extracts were combined,
washed with brine (10 mL), and then dried over anhydrous MgSO4.
Evaporation of solvent under vacuum gave an oily residue which
was purified by chromatography (eluent: EtOAc/hexane = 1:4) to
afford (SS)-butyl-phenylsulfoxide (137 mg, 0.75 mmol) in 75%
yield.
(SS)-Butyl-p-tolylsulfoxide could be obtained in 78% yield from
compound (R,SS)-1b according to the same procedure.
4.5.1. (SS)-Benzenesulfinamide (SS)-3a
Mp 101–102 °C (lit.58 102–103), ½a D25
ꢃ
¼ þ83:1 (c 1.0, acetone)
Characterization data for (SS)-butylphenylsulfoxide:
½
a 2D5
ꢃ
¼
{lit.58
½
a 2D5
ꢃ
¼ þ82:9 (acetone)}. HPLC analysis: Column: Diacel
ꢀ151:9 (c 1.3, acetone) {lit.52
½
a 2D5
ꢃ
¼ ꢀ131:5 (c 0.98, acetone)}. 1H
AD; mobile phase: hexane/ethanol = 90:10; wavelength: 235 nm;
flow rate: 0.5 mL/min; tR (retention time): 22.4 min for (SS)-isomer,
26.5 min for (SR)-isomer; purity: 99.64% for (SS), 0.36% for (SR). 1H
NMR (CDCl3) d 4.50 (s, 2H), 7.47–7.54 (m, 3H), 7.72–7.78 (m,
2H). HRMS (ESI) m/z calcd for C6H7NOSNa [M+Na]+: 164.0146,
found 164.0126. IR (KBr film) 3442, 3282, 3162, 3075, 1629,
NMR (CDCl3) d 0.92 (t, J = 7.3 Hz, 3H), 1.36–1.50 (m, 2H), 1.55–
1.64 (m, 1H), 1.68–1.78 (m, 1H), 2.80 (t, J = 7.7 Hz, 2H), 7.46–7.54
(m, 3H), 7.60–7.65 (m, 2H). MS m/z (%) 182 (M+, 17), 165 (7), 126
(100), 110 (4), 104 (7), 97 (3), 78 (41). IR (neat) 2959, 2932,
2872, 1477, 1465, 1443, 1088, 1038, 998, 750, 693 cmꢀ1
.
Characterization data for (SS)-butyl-p-tolylsulfoxide:
½
a 2D5
ꢃ
¼
1475, 1443, 1401, 1087, 1017, 995, 748, 696 cmꢀ1
.
ꢀ162:6 (c 1.8, acetone) {lit.53
½
a 2D5
ꢃ
¼ ꢀ162:3 (c 3.2, acetone)}. 1H
NMR (CDCl3) d 0.92 (t, J = 7.3 Hz, 3H), 1.36–1.49 (m, 2H), 1.54–
1.63 (m, 2H), 1.66–1.75 (m, 1H), 2.41 (s, 3H), 2.72–2.82 (m, 2H),
7.32 (d, J = 8.0 Hz, 2H), 7.51 (d, J = 8.0 Hz, 2H). MS m/z (%) 196
(M+, 20), 179 (10), 140 (100), 124 (4), 104 (9), 92 (68). IR (neat)
2959, 2930, 2871, 1597, 1494, 1463, 1400, 1380, 1087, 1038,
4.5.2. (SS)-p-Toluenesulfinamide (SS)-3b
Mp 113–114 °C (lit.59 115–116 °C), ½a 2D5
¼ þ85:5 (c 1.0, CHCl3)
ꢃ
{lit.59
½
a 2D5
ꢃ
¼ þ84:5 (c 1.0, CHCl3)}. HPLC analysis: Column: Diacel
AD; mobile phase: hexane/ethanol = 90:10; wavelength: 235 nm;
flow rate: 0.5 mL/min; tR (retention time): 21.2 min for (SS)-isomer,
27.8 min for (SR)-isomer; purity: 99.68% for (SS), 0.32% for (SR). 1H
NMR (CDCl3) d 2.41 (s, 3H), 4.49 (s, 2H), 7.30 (d, J = 7.8 Hz, 2H),
7.61 (d, J = 7.8 Hz, 2H). HRMS (ESI) m/z calcd for C7H9NOSK
[M+K]+: 194.0042, found 194.0038. IR (KBr film) 3215, 3106,
813 cmꢀ1
.
4.6.2. Determination of the absolute configurations of
compounds (R,SS)-1c and (R,SS)-1d by X-ray analysis of their
single crystals
A clear solution of compound (R,SS)-1c (0.25 g) in ether (20 mL)
was put into a flask. The flask was then sealed with a thin film of
polyvinyl chloride (PVC), and allowed to stand overnight at room
temperature. As the ether gradually evaporated, crystals of com-
pound (R,SS)-1c were formed on the bottom of the flask.
Crystals of compound (R,SS)-1d were obtained according to the
same procedure as above.
1399, 1089, 1051, 1023, 1013, 808, 721, 703 cmꢀ1
.
4.5.3. (SS)-p-Chlorobenzenesulfinamide (SS)-3c
Mp 135–136 °C (lit.48 135–137 °C), ½a 2D5
¼ þ72:3 (c 0.7, CHCl3).
ꢃ
HPLC analysis: Column: Diacel AD; mobile phase: hexane/etha-
nol = 90:10; wavelength: 235 nm; flow rate: 0.5 mL/min; tR (reten-
tion time): 24.4 min for (SS)-isomer, 43.5 min for (SR)-isomer;
purity: 99.72% for (SS), 0.28% for (SR). 1H NMR (CDCl3) d 4.42 (s,
2H), 7.49 (d, J = 8.5 Hz, 2H), 7.68 (d, J = 8.5 Hz, 2H). 13C NMR
(DMSO-d6) d 127.4, 128.6, 135.1, 147.1. HRMS (ESI) m/z calcd for
C6H7NOSCl [M+H]+: 175.9937, found 175.9915. IR (KBr film)
3197, 3103, 1572, 1472, 1396, 1081, 1048, 1023, 1009, 924, 822,
Crystal data for (R,SS)-N-benzyl-N-(1-phenylethyl)-p-chloro-
benzenesulfinamide (R,SS)-1c: C21H20ClNOS, Mr = 369.89, ortho-
rhombic, space group P212121, a = 7.4740 (7), b = 12.7861 (12),
c = 19.7011 (19) Å,
a
= 90.00°, b = 90.00°,
c = 90.00°, V = 1882.7
(3) Å3, Z = 4, DC = 1.305 Mg/m3,
l
(Mo K
a
) = 0.322 mmꢀ1, F (0 0 0) =
743, 719, 503 cmꢀ1
.
776, colorless prism, dimensions: 0.428 ꢂ 0.357 ꢂ 0.311 mm.
R = 0.0414, wR = 0.0994, goodness-of-fit on F2 = 0.988 for 3666 ob-
4.5.4. (SS)-p-Fluorobenzenesulfinamide (SS)-3d
served reflections with I > 2r(I).
Mp 155–156 °C, ½a D25
ꢃ
¼ þ80:0 (c 0.7, CHCl3). HPLC analysis: Col-
Crystal data for (R,SS)-N-benzyl-N-(1-phenylethyl)-p-fluoroben-
zenesulfinamide (R,SS)-1d: C21H20FNOS, Mr = 353.44, orthorhom-
bic, space group P212121, a = 7.4856 (14), b = 12.703 (3),
umn: Diacel AD; mobile phase: hexane/ethanol = 90:10; wave-
length: 235 nm; flow rate: 0.5 mL/min; tR (retention time):
23.2 min for (SS)-isomer, 38.5 min for (SR)-isomer; purity: 99.58%
c = 19.159 (4) Å,
a = 90.00°, b = 90.00°, c = 90.00°, V = 1821.9

R.-H. Zhu, X.-X. Shi / Tetrahedron: Asymmetry 22 (2011) 387–393
20. Kawecki, R. Tetrahedron: Asymmetry 2006, 17, 1420.
393
(6) Å3, Z = 4, DC = 1.289 Mg/m3,
l (Mo Ka
) = 0.195 mmꢀ1, F (0 0 0) =
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744, colorless prism, dimensions: 0.408 ꢂ 0.356 ꢂ 0.311 mm.
R = 0.0331, wR = 0.0743, goodness-of-fit on F2 = 0.989 for 2622
observed reflections with I > 2
Diffraction intensities were collected on a Bruker SMART CCD
diffractometer using graphite monochromated Mo K radiation
r(I).
a
(k = 0.71073 Å) at 293 K. The absorption was corrected empirically.
The structure was solved by direct methods using SHELXS-97 and re-
fined on F2 by full-matrix least-squares methods using SHELXL-97.
All non-H atoms were refined anisotropically and H-atoms
isotropically.
Crystallographic data for the structure herein have been depos-
ited with the Cambridge Crystallographic Data Centre as supple-
mentary publication numbers CCDC 797311 and 797312. Copies
of the data can be obtained, free of charge, on application to CCDC,
12 Union Road, Cambridge CB2 1EZ, UK [Tel.: +44(0) 1223 762910,
fax: +44(0) 1223 336033 or e-mail: deposit@ccdc.cam.ac.uk].
Acknowledgements
We thank the National Natural Science Foundation of China
(No. 20972048) and the Shanghai Educational Development Foun-
dation (The Dawn Program: No. 03SG27) for the financial support
of this work.
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