Enantioselective desymmetrization of meso-aziridines with aromatic thiols catalyzed by chiral bifunctional quaternary phosphonium salts derived from α-amino acids

Article abstract of DOI:10.1016/j.tet.2015.02.001

Desymmetrization of meso-aziridines with aromatic thiols was realized by using α-amino acids-derived chiral quaternary phosphonium salts catalysts to provide chiral β-amino sulfides with high yields (up to 99%) and in moderate enantioselectivities (up to

Full text of DOI:10.1016/j.tet.2015.02.001

Accepted Manuscript
Enantioselective desymmetrization of meso-aziridines with aromatic thiols catalyzed
by chiral bifunctional quaternary phosphonium salts derived from α-amino acids
Jiaxing Zhang, Dongdong Cao, Hongyu Wang, Gang Zhao, Yongjia Shang
PII:
S0040-4020(15)00134-9
10.1016/j.tet.2015.02.001
TET 26388
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 23 December 2014
Revised Date: 28 January 2015
Accepted Date: 2 February 2015
Please cite this article as: Zhang J, Cao D, Wang H, Zhao G, Shang Y, Enantioselective
desymmetrization of meso-aziridines with aromatic thiols catalyzed by chiral bifunctional quaternary
phosphonium salts derived from α-amino acids, Tetrahedron (2015), doi: 10.1016/j.tet.2015.02.001.
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ACCEPTED MANUSCRIPT
Enantioselective desymmetrization of meso-aziridines with
benzenethiols catalyzed by chiral bifunctional quaternary
phosphonium salts derived from α-amino acids
Jiaxing Zhang,a Dongdong Cao,b Hongyu Wang,b Gang Zhao,*b and Yongjia Shang*a
a
The Key Laboratory of Functional Molecular Solids, Ministry of Education, Anhui Key
Laboratory of Molecule-Based Materials, College of Chemistry and Materials Science , Anhui
Normal University , Wuhu , China
b
Key Laboratory of Synthetic Chemistry of Natural Substances, Shanghai Institute of Organic
Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, China
Fax: 0086-21-64166128; Tel: 0086-21-54925182
E-mail: shyj@mail.ahnu.edu.cn , zhaog@mail.sioc.ac.cn
R
O
NH
1f (5 mol%)
F3C
N
Ar2SH
N R
Br
+
CCl4 , -10oC
K2HPO4 (2 equiv.)
H
SHAr2
PPh2Bn
n
n
CF3
n = 1, 2
R = Ts, CO2Ar1
18 examples
up to 99% yield
up to 70% ee
1f

ACCEPTED MANUSCRIPT
Enantioselective desymmetrization of meso-aziridines with aromatic
thiols catalyzed by chiral bifunctional quaternary phosphonium salts
derived from α-amino acids
Jiaxing Zhang,a Dongdong Cao,b Hongyu Wang,b Gang Zhao,b* and Yongjia Shanga*
a
The Key Laboratory of Functional Molecular Solids, Ministry of Education, Anhui Key
Laboratory of Molecule-Based Materials, College of Chemistry and Materials Science , Anhui
Normal University , Wuhu , China
b
Key Laboratory of Synthetic Chemistry of Natural Substances, Shanghai Institute of Organic
Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, China
E-mail: shyj@mail.ahnu.edu.cn, zhaog@mail.sioc.ac.cn
Abstract: Desymmetrization of meso-aziridines with aromatic thiols was realized by
using α-amino acids-derived chiral quaternary phosphonium salts catalysts to provide
chiral β-amino sulfides with high yields (up to 99%) and in moderate
enantioselectivities (up to 70%).
Keywords: Desymmetrization, meso-aziridine, aromatic thiols, chiral quaternary
phosphonium salt, chiral β-amino sulfide.
1. Introduction
The enantioselective desymmetrization of meso-aziridines via ring opening with
various nucleophiles is a powerful synthetic method for the preparation of a variety of
substituted chiral amines.1 In this field, different kinds of nucleophiles have been used
through chiral metal catalysis2 or organocatalysis.3 In particular, the catalytic
asymmetric ring openings of meso-aziridines with sulfur-based nucleophiles provide
facile access to various chiral β-aminosulfur compounds, which are both useful
synthons in stereoselective synthesis and also have great values in pharmaceutical
industry.4 Della Sala5 and Antilla et al.6 have achieved excellent enantioselectivities in
the ring-opening of meso-aziridines with thiols (TMS-SPh and HSPh) by using chiral
phosphoric acid catalysts. Other strategies using chiral cinchona alkaloid derivatives,7
prolinols8 and guanidines9 as catalysts or using α-isothiocyanato imides10 as
sulfur-based nucleophiles have also been reported, however these methods only
obtain moderate enantioselectivities or have limitations of substrates.

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On the other hand, the asymmetric phase-transfer catalysis has been proven to be
an efficient tool in synthesizing chiral compounds.11 Although a few of chiral
phosphonium salts catalysts have been developed and used in asymmetric reactions,12
chiral phosphonium salts have been rarely studied compared to chiral ammonium salts.
Especially, the asymmetric ring-opening reaction of aziridines under phase-transfer
conditions has only been achieved by using chiral quaternary ammonium catalysts.13
Our group have focused on the development of amino acid-derived catalysts and their
applications to various enantioselective reactions.14 Recently, we have developed
chiral bifunctional phosphonium salts from amino acids as efficient asymmetric
phase-transfer catalysts, with which excellent enantioselectivity could be obtained in
aza-Henry reaction15 and Michael addition reaction16. Herein, we wish to describe the
application of chiral phosphonium salts to catalyze the desymmetrization of
meso-aziridines with thiols.
2. Results and discussion
Using the reaction between N-tosylaziridine 2a and 4-Cl benzenethiol 3a as the
model reaction, we first investigated the catalytic efficiency of different phosphonium
salt catalysts (Figure 1) bearing different chiral skeletons and differently protected
amino groups (Table 1). We found that both structural elements have significant
influence on the reaction, and the catalyst 1f derived from L-tert-Leucine with the
amide structure gave the highest enantioselectivity (entries 1-6). Then the effect of
solvent and base were examined by using 1f as a catalyst (entries 7-14). Apparently,
halohydrocarbon solvents and mild bases are favoured for the enantioselectivity, and
when CCl4 and K2HPO4 were used, an improved enantioselectivity of 60%ee was
obtained (entry 14). To further increase the enantioselectivity, we made more efforts
in modifying the structure of the catalyst 1f by varying both the substitutions of the
amide moiety and the phosphonium center (entries 15-20), but no better
enantioselectivity was obtained. When we lowered the reaction temperature to -10oC,
the product 4a was obtained in 64% ee with 94% yield, but lowering the temperature
further to -20oC led to significantly decreased ee and yield (entries 21-22). The
absolute configuration of 4a was assigned to be (1S, 2S) by comparison of the optical
rotation values with the literature data.7b

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Fig. 1 Chiral phosphonium salts
Table 1 Screening of catalysts, solvents and basesa
Entry
1
Catalyst
1a
1b
1c
1d
1e
1f
Solvent
toluene
toluene
toluene
toluene
toluene
toluene
CH2Cl2
TBME
CHCl3
CCl4
CCl4
CCl4
CCl4
CCl4
CCl4
CCl4
CCl4
Base
Yieldb(%)
90
Eec(%)
25
-5
-23
36
17
45
16
5
33% aq K2CO3
33% aq K2CO3
33% aq. K2CO3
33% aq. K2CO3
33% aq. K2CO3
33% aq. K2CO3
33% aq. K2CO3
33% aq. K2CO3
33% aq. K2CO3
33% aq. K2CO3
50% aq. K2HPO4
50% aq. Cs2CO3
KHCO3
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
88
88
91
90
90
92
94
90
95
92
97
99
99
99
99
99
1f
1f
1f
1f
1f
1f
1f
1f
36
51
60
53
56
60
30
33
58
K2HPO4
K2HPO4
K2HPO4
K2HPO4
1g
1h
1i

ACCEPTED MANUSCRIPT
18
19
CCl4
CCl4
CCl4
CCl4
CCl4
K2HPO4
K2HPO4
K2HPO4
K2HPO4
K2HPO4
99
99
99
94
40
50
55
59
64
53
1j
1k
1l
1f
1f
20
21d
22e
a
Reactions were carried out using 0.1 mmol of 2a , 0.15 mmol of 3a, 5 mol% of
catalyst 1, 0.2 mmol or 0.16 mL of base, 12 h. b Isolated yields. c Determined by chiral
stationary phase HPLC. d Reaction at -10 oC, 24 h. e Reaction at -20 oC, 48 h.
The influence of the N-protecting group of the aziridine was also investigated
with catalyst 1f or 1c (Table 2). Under the similar reaction conditions,
N-tosylaziridine 2a gave the product with 60% ee (entry 1), while N-Boc-aziridine 2b
and 4-nitrobenzoyl aziridine 2c gave very low enantioselectivity (entries 2-3).
3,5-Dinitrobenzoyl aziridine 2d and 3,5-bistrifluoromethylbenzoyl aziridine 2e gave
17% ee and 30% ee , respectively. To our surprise, the same reactions of the aziridines
2d and 2e with catalyst 1c gave the desired products in 62% ee and 33% ee,
respectively, with the opposite absolute configurations to those obtained with catalyst
1f (entries 4-5).
Table 2 Screening of N-substituted aziridines 2a
Entry
1
2 (R)
Catalyst
Time (h) Yieldb(%)
Eec (%)
60
2a (Ts)
1f
9
99
2
3
2b (Boc)
2c (4-nitrobenzoyl)
9
12
99
95
0
20
1f
1f
11
99
17
1f
2d
4
5
(3,5-dinitrobenzoyl)
20
98
-62
1c
18
18
99
99
30
1f
2e
(3,5-bisCF3benzoyl)
-33
1c
b
a Reactions were carried out using 0.1 mmol of 2, 0.15 mmol 3a, 5 mol% of 1.
Isolated yields. c Determined by chiral stationary phase HPLC.
Next, a series of aromatic thiols 3 were subjected to the reaction with

ACCEPTED MANUSCRIPT
N-tosylaziridine 2a under the optimized conditions [catalyst 1f (5 mol%), CCl4,
o
K2HPO4 (2 equiv), -10 C] (Table 3). In general, excellent yields and moderate
enantioselectivities were obtained. For thiols 3 bearing differently substituted benzene
groups, those with electron-donating substituents provided relatively lower ee values
and yields (entries 5, 6 and 12) than those with electron-withdrawing ones. Notably, a
meta effect was observed: m-substituted aryl thiols gave slightly higher ee values
(70%) (entries 3 and 10). Moreover, naphthyl-1-thiol 3n and naphthyl-2-thiol 3o gave
the desired products in similarly excellent yields and moderate enantioselectivities
(entries 14 and 15). However, the use of heteroaryl thiol 3m led to significantly
reduced yield and enantioselectivity, in which only 60% yield and 30% ee were
obtained (entry 13). To our delight, the useful aziridine 2f derived from cyclopentene
was also worked to provide comparable results (entry 16).
In addition, the o-bromo-substituted product 4k was subjected to a Pd-catalyzed
cyclization to provide the phenothiazine product 5 in 70% yield without appreciable
decrease in the ee (Scheme 3).
Table 3 Scope study with different thiols 3a
Yieldb
(%)
98
83
97
98
70
80
96
98
94
94
90
93
60
Eec
(%)
64
59
62
70
56
57
62
60
67
70
62
44
30
Entry
2
3
Ar
4
1
2
3
4
5
6
7
8
9
10
11
12
13
4-ClC6H4
Ph
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
3a
3b
3c
3d
3e
3f
3g
3h
3i
4a
4b
4c
4d
4e
4f
4g
4h
4i
2-ClC6H4
3-ClC6H4
4-CH3C6H4
4-OCH3C6H4
4-FC6H4
4-NO2C6H4
4-BrC6H4
3-BrC6H4
2-BrC6H4
2-NH2C6H4
4-pyridyl
3j
3k
3l
4j
4k
4l
3m
4m

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14
15
1-naphthyl
2-naphthyl
Ph
90
92
95
98
54
57
51
2a
2a
2f
3n
3o
3b
3a
4n
4o
4p
4q
16
17d
Ph
-62
2d
a Reactions were carried out using 0.1 mmol of 2, 0.15 mmol of 3, 5 mol% of 1f, 24 h.
Isolated yields. c Determined by chiral stationary phase HPLC. 5 mol% of catalyst
b
d
1c was used.
Ts
N
NHTs
S
Pd(OAc)2 (20 mol%)
( )-BINAP (40 mol%)
K2CO3 (2.5 equiv)
toluene, reflux, 4h
S
Br
5
ee = 61%
yield = 70%
4k
ee = 62%
Scheme 3 Transformation of the compound 4k
3. Conclusion
In conclusion, we have developed a new approach for the desymmetrization of
meso-aziridines with aromatic thiols by using chiral bifunctional quaternary
phosphonium salts as catalysts. A series of β-amino sulfides were obtained in high
yields and in moderate enantioselectivities. This work expands the application scope
of asymmetric phase-transfer catalysis with α-amino acid-derived chiral phosphonium
salts.
4. Experimental
4.1 General information
1
The H NMR spectra were recorded on a Bruker (400 MHz) spectrometer. All
chemical shifts (δ) were given in ppm. Data were reported as follows: chemical shift,
integration, multiplicity (s = single, d = doublet, t = triplet, q = quartet, br = broad, m
= multiplet) and coupling constants (Hz). 13C NMR spectra were recorded on a
DPX-400 (400 MHz). Flash column chromatography was performed using H silica
gel. For thin-layer chromatography (TLC), silica gel plates (HSGF 254) were used
and compounds were visualized by irradiation with UV light. Analytical high
performance liquid chromatography (HPLC) was carried out on SHIMADZU
equipment using chiral columns. Melting points were determined on a SGW X-4
melting point apparatus and were uncorrected. Optical rotations were measured on a
JASCO P-1010 Polarimeter at λ = 589 nm. IR spectra were recorded on a
Perkin-Elmer 983G instrument. Mass spectra analysis was performed on API 200
LC/MS system (Applied Biosystems Co. Ltd.).

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All reagents purchased from commercial sources were purified by standard
techniques prior to use. Aziridines were prepared according to literature procedures.2b,
3
Preparation and characterization of the catalysts 1a-1e were reported in the
published literatures. 15
4.2 Preparation of catalysts 1f to 1l
To a solution of the corresponding α-amino acid-derived bifunctional phosphine
(1.0 equiv) in anhydrous toluene was added the corresponding benzylic halide (1.2
o
equiv), and the resulting mixture was stirred at 110 C for 8 h. Then the mixture was
allowed to cool to ambient temperature and concentrated under reduced pressure. The
crude mixture was purified by flash column chromatography to afford the desired
phase transfer catalyst (CH2Cl2/MeOH = 20 : 1).
4.2.1ꢀ(S)-Benzyl(2-(3,5-bis(trifluoromethyl)benzamido)-3,3-dimethylbutyl)diphenyl
phosphonium bromide(1f).
Yield: 90%; White solid. m.p. = 137-138oC; [α]D24 = 48.6 (c = 1.0, CH2Cl2); 1H-NMR
(400 MHz, CDCl3): δ 9.22 (bs, 1H), 8.53 (s, 2H), 7.90-7.93 (m, 3H), 7.65-7.69 (m,
3H), 7.46-7.54 (m, 5H), 7.11-7.21 (m, 4H), 6.91-6.93 (m, 2H), 5.32-5.34 (m, 1H),
4.89 (d, J = 14.4 Hz, 1H), 4.44-4.53 (m, 1H), 4.10-4.11 (m, 1H), 2.57-2.64 (m, 1H),
13
1.00 (s, 9H); C-NMR (100 MHz, CDCl3): δ 164.2, 134.7, 134.3 (d, JC-P = 3.1 Hz),
134.0 (d, JC-P = 9.5 Hz), 133.8 (d, JC-P = 5.0 Hz), 131.2 (q, JC-F = 36 Hz), 130.3 (d,
JC-P = 5.5 Hz), 129.8 (d, JC-P = 12.3 Hz), 129.6 (d, JC-P = 12.3 Hz), 128.8 (d, JC-P = 2.9
Hz), 128.6 (d, JC-P = 2.5 Hz), 128.4 (d, JC-P = 3.5 Hz), 127.1, 127.0, 124.7, 123.0 (q,
JC-F = 271.7 Hz), 117.6, 117.0, 116.7, 116.1, 52.3 (d, JC-P = 5.6 Hz), 37.3 (d, JC-P
=
11.7 Hz), 30.5, 30.1, 26.4, 22.5, 22.0; 31P-NMR (163 MHz, CDCl3): δ 25.2; 19F-NMR
(282 MHz, CDCl3): δ -62.5; IR (Neat) 3227, 2963, 1662, 1539, 1438, 1337, 1279,
1181, 1136, 1134, 803, 743, 700; HRMS(MALDI): calcd. for [M-Br]+ (C34H33NOF6P)
requires 616.2204, found 616.2197.
4.2.2.
(S)-Benzyl(3,3-dimethyl-2-(4-nitrobenzamido)butyl)diphenylphosphonium
bromide(1g)
24
Yield: 90%; yellow solid. m.p. = 153-154oC; [α]D = 222.6 (c = 0.5, CH2Cl2);
1H-NMR (400 MHz, CDCl3): δ 8.96 (d, J = 9.2 Hz, 1H), 8.29 (d, J = 8.8 Hz, 2H),
8.20 (d, J = 8.8 Hz, 2H), 7.89-7.94 (m, 2H), 7.62-7.69 (m, 3H), 7.53-7.55 (m, 8H),
7.16-7.20 (m, 1H), 7.09 (t, J = 7.6 Hz, 2H), 6.88-6.90 (m, 2H), 5.26-5.33 (m, 1H),
4.98 (t, J = 14.2 Hz, 1H), 4.37-4.46 (m, 1H), 4.03-4.10 (m, 1H), 2.55-2.62 (m, 1H),
0.96 (s, 9H); 13C-NMR (100 MHz, CDCl3): δ 164.9, 149.3, 137.9, 134.7 (d, JC-P = 2.6
Hz), 134.5 (d, JC-P = 2.9 Hz), 133.9 (d, JC-P = 8.5 Hz), 133.7 (q, JC-P = 11.1 Hz), 130.3
(d, JC-P = 5.5 Hz), 129.8 (d, JC-P = 2.4 Hz), 129.7 (d, JC-P = 2.6 Hz), 129.4, 128.8 (d,
JC-P = 3.0 Hz), 128.3 (d, JC-P = 3.6 Hz), 127.1, 127.0, 123.0, 117.2, 117.0, 116.4,
116.2, 52.1 (d, JC-P = 5.5 Hz), 37.2 (d, JC-P = 11.8 Hz), 29.9, 29.5, 26.3, 22.9, 22.4;
31P-NMR (163 MHz, CDCl3): δ 26.1; IR (Neat) 3240, 3057, 2964, 1659, 1601, 1524,
1489, 1341, 1110, 1015, 841, 744; HRMS(MALDI): calcd. for [M-Br]+ (C32H34N2O3P)
requires 525.2307, found 525.2286.
4.2.3 .(S)-Benzyl(2-(3,5-dinitrobenzamido)-3,3-dimethylbutyl)diphenylphosphonium
bromide(1h)
24
Yield: 88%; yellow solid. m.p. = 166-167oC; [α]D = 99.5 (c = 0.5, CH2Cl2);
1H-NMR (400 MHz, CDCl3): δ 9.48 (d, J = 8.8 Hz, 1H), 9.08 (s, 2H), 9.03 (s, 1H),

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7.92-7.97 (m, 2H), 7.51-7.79 (m, 8H), 7.07-7.18 (m, 3H), 6.89-6.90 (m, 2H),
4.85-5.01 (m, 2H), 4.23-4.49 (m, 2H), 3.00 (t, J = 14.4 Hz, 1H), 2.51 (s, 1H), 1.02 (s,
13
9H); C-NMR (100 MHz, CDCl3): δ 163.2, 148.0, 136.5, 134.8 (d, JC-P = 3.1 Hz),
134.5 (d, JC-P = 2.7 Hz), 134.1 (d, JC-P = 9.5 Hz), 133.8 (q, JC-P = 9.0 Hz), 130.4 (d,
JC-P = 5.6 Hz), 130.0, 129.9 (d, JC-P = 0.8 Hz), 129.8, 128.9 (d, JC-P = 3.1 Hz), 128.5,
128.4, 127.0, 126.9, 120.9, 117.4, 117.0, 116.6, 116.1, 110.0, 52.6 (d, JC-P = 5.5 Hz),
31
37.5 (d, JC-P = 11.5 Hz), 30.4, 30.0, 26.4, 22.6, 22.1; P-NMR (163 MHz, CDCl3): δ
25.9; IR (Neat) 3220, 2962, 1664, 1541, 1343, 1110, 1076, 803, 729, 689;
HRMS(MALDI): calcd. for [M-Br]+ (C32H33N3O5P) requires 570.2154, found
570.2167.
4.2.4.(S)-(2-(3,5-Bis(trifluoromethyl)benzamido)-3,3-dimethylbutyl)(4-methoxybenzy
l)diphenylphosphonium bromide(1i)
Yield: 94%; White solid. m.p. = 131-133oC; [α]D24 = 38.7 (c = 0.5, CH2Cl2); 1H-NMR
(400 MHz, CDCl3): δ 9.16 (d, J = 4.4 Hz, 1H), 8.51 (s, 2H), 7.88-7.92 (m, 3H),
7.64-7.69 (m, 3H), 7.54-7.55 (m, 2H), 7.42-7.43 (m, 3H), 6.82-6.85 (m, 2H), 6.65 (d,
J = 8.4 Hz, 2H), 5.25-5.32 (m, 1H), 4.78-4.86 (m, 1H), 4.43-4.52 (m, 1H), 4.00-4.05
13
(m, 1H), 3.72 (s, 3H), 2.59 (t, J = 14.2 Hz, 1H), 1.01 (s, 9H); C-NMR (100 MHz,
CDCl3): δ 164.2, 159.5 (d, JC-P = 3.6 Hz), 134.6, 134.2 (d, JC-P = 2.9 Hz), 134.1, 134.0,
133.8, 133.7, 131.5 (d, JC-P = 5.4 Hz), 131.2 (q, JC-F = 33.5 Hz), 129.9, 129.8, 129.7,
129.5, 128.6 (d, JC-P = 2.2 Hz), 124.7, 123.0 (q, JC-F = 271.8 Hz), 118.4, 118.3, 117.7,
117.2, 116.9, 116.3, 114.3 (d, JC-P = 2.9 Hz), 55.1, 52.3 (d, JC-P = 5.6 Hz), 37.4 (d, JC-P
= 11.6 Hz), 29.9, 29.4, 26.4, 22.2, 21.7; 31P-NMR (163 MHz, CDCl3): δ 24.4;
19F-NMR (282 MHz, CDCl3): δ -62.5; IR (Neat) 3225, 3050, 2963, 1662, 1539, 1514,
1439, 1280, 1181, 1136, 1019, 801, 743, 681; HRMS(MALDI): calcd. for [M-Br]+
(C35H35NO2F6P) requires 646.2310, found 646.2288.
4.2.5.(S)-(2-(3,5-Bis(trifluoromethyl)benzamido)-3,3-dimethylbutyl)(3,5-bis(trifluoro
methyl)benzyl)diphenylphosphonium bromide(1j)
Yield: 94%; White solid. m.p. = 147-149oC; [α]D24 = 47.7 (c = 0.3, CH2Cl2); 1H-NMR
(400 MHz, CDCl3): δ 9.09-9.12 (m, 1H), 8.53 (s, 2H), 7.95-8.01 (m, 3H), 7.54-7.76
(m, 9H), 7.29 (s, 2H), 5.43-5.50 (m, 2H), 4.39-4.48 (m, 2H), 2.78-2.88 (m, 1H), 0.99
(s, 9H); 13C-NMR (100 MHz, CDCl3): δ 164.3, 135.4 (d, JC-P = 2.6 Hz), 134.8 (d, JC-P
= 3.0 Hz), 134.7, 134.2, 134.1, 134.0, 133.9, 132.1 (d, JC-P = 3.2 Hz), 131.8 (d, JC-P
3.3 Hz), 131.4 (q, JC-F = 33.6 Hz), 130.9, 130.8, 130.6, 130.5 (d, JC-P = 4.8 Hz), 130.3,
130.2, 130.0, 129.8, 128.5 (d, JC-P = 2.3 Hz), 124.9 (d, JC-P = 3.3 Hz), 123.0 (q, JC-F
=
=
271.6 Hz), 122.4 (q, JC-F = 271.5 Hz), 121.9 (d, JC-P = 3.6 Hz), 115.7, 115.5, 114.9,
114.6, 52.4 (d, JC-P = 5.8 Hz), 37.4 (d, JC-P = 11.9 Hz), 30.8, 30.3, 23.5, 23.0;
31P-NMR (163 MHz, CDCl3): δ 27.7; 19F-NMR (282 MHz, CDCl3): δ -62.6, -63.2; IR
(Neat) 3237, 2969, 2925, 1666, 1374, 1279, 1179, 1135, 903, 801 ꢁ 682;
HRMS(MALDI): calcd. for [M-Br]+ (C36H31NOF12P) requires 752.1952, found
752.1939.
4.2.6.(S)-(2-(3,5-Bis(trifluoromethyl)benzamido)-3,3-dimethylbutyl)(4-nitrobenzyl)di
phenylphosphonium bromide(1k)
Yield: 92%; White solid. m.p. = 145-146oC; [α]D24 = 51.9 (c = 1.0, CH2Cl2); 1H-NMR
(400 MHz, CDCl3): δ 9.09 (d, J = 8.4 Hz, 1H), 8.50 (s, 2H), 7.93-8.02 (m, 4H),
7.61-7.79 (m, 5H), 7.48-7.49 (m, 3H), 7.18 (d, J = 2.0 Hz, 1H), 7.16 (d, J = 2.0 Hz,
1H), 5.37-5.53 (m, 2H), 4.22-4.47 (m, 2H), 2.75 (t, J = 14.4 Hz, 1H), 0.99 (s, 9H);
13C-NMR (100 MHz, CDCl3): δ 164.1, 147.4 (d, JC-P = 4.2 Hz), 135.7, 135.6, 135.2 (d,

ACCEPTED MANUSCRIPT
JC-P = 2.8 Hz), 134.8, 134.5 (d, JC-P = 2.7 Hz), 134.2, 134.1, 134.0, 133.99, 131.7,
131.5, 131.42, 131.40, 131.1, 130.7, 130.1 (d, JC-P = 12.2 Hz), 129.7 (d, JC-P = 12.5
Hz), 128.8, 128.7, 128.4 (d, JC-P = 2.9 Hz), 124.8, 123.6 (d, JC-P = 3.0 Hz), 123.0 (q,
JC-F = 271.7 Hz), 116.2, 115.7, 115.4, 114.9, 52.4 (d, JC-P = 5.7 Hz), 37.3 (d, JC-P
=
11.8 Hz), 31.0, 30.5, 26.3, 26.1, 23.5, 23.1; 31P-NMR (163 MHz, CDCl3): δ 26.6;
19F-NMR (282 MHz, CDCl3): δ -62.5; IR (Neat) 3232, 3056, 2963, 1666, 1526, 1439,
1347, 1280, 1182, 1136, 1017, 859, 801ꢁ 743, 698ꢂHRMS(MALDI): calcd. for
[M-Br]+ (C34H32N2F6O3P) requires 661.2055, found 661.2045.
4.2.7.(S)-(2-(3,5-Bis(trifluoromethyl)benzamido)-3,3-dimethylbutyl)(naphthalen-1-yl
methyl)diphenylphosphonium bromide(1l)
Yield: 90%; White solid. m.p. = 133-134oC; [α]D24 = 41.9 (c = 0.5, CH2Cl2); 1H-NMR
(400 MHz, CDCl3): δ 9.36 (br, 1H), 8.55 (s, 2H), 7.91-7.95 (m, 3H), 7.36-7.66 (m,
14H), 6.97 (d, J = 8.8 Hz, 1H), 5.40-5.43 (m, 1H), 4.98-5.06 (m, 1H), 4.26-4.27 (m,
13
1H), 2.62 (t, J = 14.0 Hz, 1H), 0.99 (s, 9H); C-NMR (100 MHz, CDCl3): δ 164.3,
134.7, 134.3 (d, JC-P = 3.0 Hz), 134.1 (d, JC-P = 9.6 Hz), 133.8 (d, JC-P = 8.9 Hz),
132.8 (d, JC-P = 3.3 Hz), 132.5 (d, JC-P = 2.7 Hz), 131.3 (q, JC-F = 33.6 Hz), 130.0 (d,
JC-P = 7.2 Hz), 129.9, 129.7 (d, JC-P = 12.4 Hz), 128.7, 128.6 (d, JC-P = 2.5 Hz), 127.5
(d, JC-P = 1.6 Hz), 127.4 (d, JC-P = 1.4 Hz), 127.35, 127.31, 126.69, 126.67, 124.8,
124.3, 124.2, 123.2 (q, JC-F = 271.8 Hz), 117.6, 117.1, 116.8, 116.3, 52.4 (d, JC-P = 5.7
31
Hz), 37.4 (d, JC-P = 11.7 Hz), 30.8, 30.4, 26.4, 26.2, 22.5, 22.0; P-NMR (163 MHz,
19
CDCl3): δ 25.2; F-NMR (282 MHz, CDCl3): δ -62.5; IR (Neat) 3229, 2963, 2926,
2907, 1663, 1541, 14383, 1363, 1279, 1181, 1136, 821, 742, 681; HRMS(MALDI):
calcd. for [M-Br]+ (C38H35NOF6P) requires 666.2360, found 666.2347.
4.3 General procedure for the enantioselective desymmetrization of
meso-aziridines with benzenethiols
To a suspension of the corresponding benzenethiol 3 (0.15 mmol) in CCl4 (1.0
ml) was added catalyst 1f (5 mol%) and K2HPO4 (0.2 mmol) sequentially, and the
o
resulting mixture was stirred at -10 C for 5 min. Then aziridine 2 (0.1 mmol) was
o
added. The resulting suspension was vigorously stirred at -10 C for 24 h, and then
directly purified by column chromatography (silica gel: petroleum ether/AcOEt =
10:1 – 5:1) on silica gel to afford the product 4.
4.3.1. N-((1R,2R)-2-((4-Chlorophenyl)thio)cyclohexyl)-4-methylbenzenesulfonamide
(4a)17
25
Yield: 94%; white solid. Enantiomeric excess: 64%, [α]D = -20.2 (c = 2.7, CHCl3),
determined by HPLC (Chiralpak AD-H column, hexane/i-PrOH 9:1, flow rate 0.7
ml/min, tminor = 23.1 min, tmajor = 21.1 min, λ = 254 nm); 1H-NMR (400 MHz, CDCl3):
δ 7.74 (d, J = 8.0 Hz, 2H), 7.28 (d, J = 8.0 Hz, 2H), 7.20-7.26 (m, 4H), 5.32-5.37 (m,
1H), 2.92-3.01 (m, 2H), 2.43 (s, 3H), 2.17-2.20 (m, 1H), 1.98-2.01 (m, 1H), 1.26-1.69
(m, 6H).
4.3.2. N-((1R,2R)-2-(Phenylthio)cyclohexyl)-3,5-bis(trifluoromethyl)benzamide (4b)
17
28
Yield: 85%; white solid. Enantiomeric excess: 59%, [α]D = -11.3 (c = 1.4, CHCl3),
determined by HPLC (Chiralpak AD-H column, hexane/i-PrOH 85:15, flow rate 1.0
ml/min, tminor = 12.2 min, tmajor = 11.1 min, λ = 254 nm); 1H-NMR (400 MHz, CDCl3):
δ 7.74 (d, J = 8.0 Hz, 2H), 7.28 (d, J = 8.0 Hz, 2H), 7.22-7.26 (m, 5H), 5.25 (d, J =

ACCEPTED MANUSCRIPT
3.6 Hz, 1H), 2.88-3.00 (m, 2H), 2.43 (s, 3H), 2.25-2.27 (m, 1H), 2.00-2.03 (m, 1H),
1.57-1.62 (m, 3H), 1.25-1.42 (m, 3H); MS (ESI): m/z 384.1 (M++Na).
4.3.3. N-((1R,2R)-2-((2-Chlorophenyl)thio)cyclohexyl)-4-methylbenzenesulfonamide
(4c) 17
26
Yield: 95%; white solid. Enantiomeric excess: 62%, [α]D = -4.1 (c = 1.85, CHCl3),
determined by HPLC (Phenomenex Cellulose-2 column, hexane/i-PrOH 9:1, flow rate
1
1.0 ml/min, tminor = 28.8 min, tmajor = 23.0 min, λ = 254 nm); H-NMR (400 MHz,
CDCl3): δ 7.67 (d, J = 8.0 Hz, 2H), 7.28-7.33 (m, 2H), 7.21 (d, J = 8.0 Hz, 2H),
7.10-7.12 (m, 2H), 5.08-5.10 (m, 1H), 3.01-3.02 (m, 2H), 2.35 (s, 3H), 2.19-2.21 (m,
1H), 1.95-1.98 (m, 1H), 1.41-1.57 (m, 3H), 1.19-1.29 (m, 3H); MS (ESI): m/z 418.0
(M++Na).
4.3.4. N-((1R,2R)-2-((3-Chlorophenyl)thio)cyclohexyl)-4-methylbenzenesulfonamide
(4d)
27
Yield: 95%; white solid. m.p. = 71-73oC. Enantiomeric excess: 70%, [α]D = 1.99 (c
= 1.85, CHCl3), determined by HPLC (Chiralpak AD-H column, hexane/i-PrOH
85:15, flow rate 1.0 ml/min, tminor = 11.1 min, tmajor = 9.9 min, λ = 254 nm); 1H-NMR
(400 MHz, CDCl3): δ 7.67 (d, J = 8.0 Hz, 2H), 7.22 (d, J = 8.0 Hz, 2H), 7.08-7.12 (m,
4H), 4.98-5.01 (m, 1H), 2.91-2.98 (m, 2H), 2.36 (s, 3H), 2.15-2.17 (m, 1H), 1.96-1.98
(m, 1H), 1.53-1.55 (m, 1H), 1.19-1.37 (m, 5H); 13C-NMR (100 MHz, CDCl3): δ 143.4,
137.5, 135.7, 134.6, 131.8, 130.2, 130.0, 129.7, 127.4, 127.2, 55.1, 51.0, 32.0, 31.2,
24.2, 23.1, 21.6; IR (Neat) 3278, 2932, 2870, 1580, 1543, 1459, 1330, 1158, 1093,
820, 778, 670, 569, 551; HRMS(MALDI): calcd. for [M+Na]+ (C19H22NClS2O2)
requires 418.0678, found 418.0682.
4.3.5. 4-Methyl-N-((1R,2R)-2-(p-tolylthio)cyclohexyl)benzenesulfonamide (4e)17
28
Yield: 80%; white solid. Enantiomeric excess: 57%, [α]D = -14.6 (c = 1.3, CHCl3),
determined by HPLC (Chiralpak AS-H column, hexane/i-PrOH 1:4, flow rate 0.3
ml/min, tminor = 86.5 min, tmajor = 41.7 min, λ = 254 nm); 1H-NMR (400 MHz, CDCl3):
δ 7.68 (d, J = 8.0 Hz, 2H), 7.23 (d, J = 8.0 Hz, 2H), 7.08 (d, J = 8.0 Hz, 2H), 6.98 (d,
J = 8.0 Hz, 2H), 5.16-5.17 (m, 1H), 2.83-2.85 (m, 1H), 2.68-2.71 (m, 1H), 2.37 (s,
3H), 2.26 (s, 3H), 1.50-1.54 (m, 1H), 1.15-1.28 (m, 6H); MS (ESI): m/z 398.2
(M++Na).
4.3.6.
N-((1R,2R)-2-((4-Methoxyphenyl)thio)cyclohexyl)-4-methylbenzenesulfonamide
(4f)17
Yield: 70%; white solid. Enantiomeric excess: 56%, [α]D28 = -21.3 (c = 1.05, CHCl3),
determined by HPLC (Chiralpak AS-H column, hexane/i-PrOH 1:4, flow rate 0.3
ml/min, tminor = 80.1 min, tmajor = 61.7 min, λ = 254 nm); 1H-NMR (400 MHz, CDCl3):
δ 7.69 (d, J = 8.0 Hz, 2H), 7.23 (d, J = 8.0 Hz, 2H), 7.12 (d, J = 8.8 Hz, 2H), 6.70 (d,
J = 8.8 Hz, 2H), 5.21-5.24 (m, 1H), 3.73 (s, 3H), 2.79-2.84 (m, 1H), 2.56-2.60 (m,
1H), 2.37 (s, 3H), 2.23-2.26 (m, 1H), 1.88-1.93 (m, 1H), 1.50-1.54 (m, 1H),
13
1.14-1.24(m, 5H); C-NMR (100 MHz, CDCl3): δ 159.9, 143.3, 137.6, 136.4, 129.7,
127.3, 122.3, 114.5, 55.3, 52.3, 32.5, 31.8, 24.9, 23.5, 21.6ꢂHRMS(MALDI): calcd.
for [M+Na]+ (C20H25NS2O3) requires 414.1174, found 414.1173.
4.3.7. N-((1R,2R)-2-((4-Fluorophenyl)thio)cyclohexyl)-4-methylbenzenesulfonamide
(4g)17

ACCEPTED MANUSCRIPT
27
Yield: 99%; white solid. Enantiomeric excess: 61%, [α]D = -17.6 (c = 2.1, CHCl3),
determined by HPLC (Phenomenex Cellulose-2 column, hexane/i-PrOH 95:5, flow
rate 0.7 ml/min, tminor = 74.6 min, tmajor = 61.7 min, λ = 254 nm); 1H-NMR (400 MHz,
CDCl3): δ 7.78 (d, J = 8.0 Hz, 2H), 7.32 (d, J = 8.0 Hz, 2H), 7.28 (d, J = 7.6 Hz, 2H),
6.97 (t, J = 8.8 Hz, 2H), 5.29-5.31 (m, 1H), 2.98-3.00 (m, 1H), 2.81-2.86 (m, 1H),
2.47 (s, 3H), 2.26-2.27 (m, 1H), 1.98-2.00 (m, 1H), 1.60-1.64 (m, 2H), 1.26-1.40(m,
4H); MS (ESI): m/z 402.0 (M++Na).
4.3.8. 4-Methyl-N-((1R,2R)-2-((4-nitrophenyl)thio)cyclohexyl)benzenesulfonamide
(4h)
Yield: 99%; yellow solid. m.p. = 64-65oC. Enantiomeric excess: 60%, [α]D26 = 58.2 (c
= 2.35, CHCl3), determined by HPLC (Chiralpak AD-H column, hexane/i-PrOH 4:1,
flow rate 1.0 ml/min, tminor = 20.4 min, tmajor = 16.6 min, λ = 254 nm); 1H-NMR (400
MHz, CDCl3): δ 8.12 (d, J = 8.8 Hz, 2H), 7.76 (d, J = 8.0 Hz, 2H), 7.36 (d, J = 8.8 Hz,
2H), 7.32 (d, J = 8.0 Hz, 2H), 5.03 (d, J = 6.4 Hz, 1H), 3.24-3.38 (m, 2H), 2.47 (s,
13
3H), 2.16-2.17 (m, 2H), 1.60-1.65 (m, 4H), 1.29-1.45(m, 2H); C-NMR (100 MHz,
CDCl3): δ 145.5, 143.7ꢁ137.,5, 129.7, 128.4, 127.1, 123.9, 54.7, 49.1, 31.3, 30.4, 23.6,
22.7, 21.5; IR (Neat) 3276, 2932, 1577, 1510, 1337, 1157, 1093, 853, 814, 742, 666,
572; HRMS(MALDI): calcd. for [M+Na]+ (C19H22N2S2O4) requires 429.0919, found
429.0900.
4.3.9. N-((1R,2R)-2-((4-Bromophenyl)thio)cyclohexyl)-4-methylbenzenesulfonamide
(4i)17
28
Yield: 93%; white solid. Enantiomeric excess: 67%, [α]D = 4.28 (c = 2.0, CHCl3),
determined by HPLC (Chiralpak AD-H column, hexane/i-PrOH 85:15, flow rate 1.0
ml/min, tminor = 14.1 min, tmajor = 12.0 min, λ = 254 nm); 1H-NMR (400 MHz, CDCl3):
δ 7.66 (d, J = 8.0 Hz, 2H), 7.27 (d, J = 8.8 Hz, 2H), 7.20 (d, J = 8.0 Hz, 2H), 7.05 (d,
J = 8.8 Hz, 2H), 5.29 (d, J = 4.8 Hz, 1H), 2.87-2.94 (m, 2H), 2.36 (s, 3H), 2.10-2.12
(m, 1H), 1.91-1.97 (m, 1H), 1.49-1.51 (m, 2H), 1.29-1.35(m, 1H), 1.18-2.00 (m, 3H);
MS (ESI): m/z 462.0 (M++Na).
4.3.10.
N-((1R,2R)-2-((3-Bromophenyl)thio)cyclohexyl)-4-methylbenzenesulfonamide (4j)
Yield: 94%; white solid. m.p. = 80-82oC. Enantiomeric excess: 71%, [α]D26 = 3.5 (c =
2.0, CHCl3), determined by HPLC (Phenomenex Cellulose-2 column, hexane/i-PrOH
1
9:1, flow rate 1.0 ml/min, tminor = 26.7 min, tmajor = 20.9 min, λ = 254 nm); H-NMR
(400 MHz, CDCl3): δ 7.66 (d, J = 8.0 Hz, 2H), 7.39 (s, 1H), 7.31 (d, J = 8.0 Hz, 1H),
7.22 (d, J = 8.0 Hz, 2H), 7.13-7.19 (m, 1H), 7.05 (t, J = 8.0 Hz, 1H), 4.94 (d, J = 4.4
Hz, 1H), 2.91-2.99 (m, 2H), 2.36 (s, 3H), 2.15-2.17 (m, 1H), 1.93-1.97 (m, 1H),
1.53-1.55 (m, 1H), 1.33-1.35 (m, 1H), 1.19-1.23 (m, 4H); 13C-NMR (100 MHz,
CDCl3): δ 143.4, 137.4, 136.1, 134.6, 130.7, 130.3, 129.7, 127.2, 122.7, 55.1, 51.1,
32.0, 31.2, 24.2, 23.1, 21.6; IR (Neat) 3276, 2934, 2857, 1574, 1556, 1459, 1327,
1156, 1093, 813, 778, 754, 666, 572, 551; HRMS(MALDI): calcd. for [M+Na]+
(C19H22NBrS2O2) requires 462.0173, found 462.0170.
4.3.11.
N-((1R,2R)-2-((2-Bromophenyl)thio)cyclohexyl)-4-methylbenzenesulfonamide (4k)
Yield: 90%; white solid. m.p. = 93-95oC. Enantiomeric excess: 63%, [α]D22 = -6.48 (c
= 1.13, CH2Cl2), determined by HPLC (Chiralpak AD-H column, hexane/i-PrOH 9:1,

ACCEPTED MANUSCRIPT
flow rate 1.0 ml/min, tminor = 20.6 min, tmajor = 15.3 min, λ = 254 nm); 1H-NMR (400
MHz, CDCl3): δ 7.67 (d, J = 8.0 Hz, 2H), 7.50 (d, J = 8.0 Hz, 1H), 7.28-7.30 (m, 1H),
7.14-7.22 (m, 3H), 7.02 (t, J = 8.0 Hz, 1H), 5.12-5.19 (m, 1H), 3.00-3.03 (m, 2H),
2.35 (s, 3H), 2.20-2.22 (m, 1H), 1.95-1.98 (m, 1H), 1.43-1.55 (m, 3H), 1.18-1.31 (m,
3H); 13C-NMR (100 MHz, CDCl3): δ 143.4, 137.1, 135.3, 133.4, 132.8, 129.7, 128.4,
127.9, 127.3, 127.0, 55.1, 50.4, 32.3, 31.1, 24.2, 23.1, 21.6; IR (Neat) 3277, 2934,
2857, 1448, 1327, 1157, 1093, 1019, 895, 814, 749, 667, 571, 551; HRMS(MALDI):
calcd. for [M+H]+ (C19H23NBrS2O2) requires 440.0343, found 440.0348.
4.3.12.
N-((1R,2R)-2-((2-Aminophenyl)thio)cyclohexyl)-4-methylbenzenesulfonamide (4l)17
26
Yield: 93%; white solid. Enantiomeric excess: 44%, [α]D = -26.5 (c = 1.7, CHCl3),
determined by HPLC (Chiralpak AD-H column, hexane/i-PrOH 4:1, flow rate 1.0
ml/min, tminor = 27.4 min, tmajor = 19.1 min, λ = 254 nm); 1H-NMR (400 MHz, CDCl3):
δ 7.68 (d, J = 8.0 Hz, 2H), 7.21 (d, J = 8.0 Hz, 1H), 7.03-7.10 (m, 2H), 7.63 (d, J =
8.0 Hz, 2H), 6.55 (t, J = 7.6 Hz, 1H), 5.12-5.16 (m, 1H), 4.26 (s, 2H), 2.97-3.00 (m,
1H), 2.63-2.69 (m, 1H), 2.35 (s, 3H), 2.10-2.11 (m, 1H), 1.88-1.89 (m, 1H), 1.48-1.54
(m, 2H), 1.28-1.37 (m, 1H), 1.08-1.18 (m, 3H); MS (ESI): m/z 377.0 (M++H).
4.3.13.
4-Methyl-N-((1R,2R)-2-(pyridin-4-ylthio)cyclohexyl)benzenesulfonamide
(4m)
Yield: 60%; yellow solid. m.p. = 116-118oC. Enantiomeric excess: 30%, [α]D26 = 58.2
(c = 2.35, CHCl3), determined by HPLC (Chiralpak AD-H column, hexane/i-PrOH
1
4:1, flow rate 1.0 ml/min, tminor = 15.5 min, tmajor = 11.6 min, λ = 254 nm); H-NMR
(400 MHz, CDCl3): δ 8.41 (d, J = 6.0 Hz, 2H), 7.76 (d, J = 8.0 Hz, 2H), 7.20 (d, J =
8.0 Hz, 2H), 7.11 (d, J = 6.0 Hz, 2H), 4.98 (d, J = 6.0 Hz, 1H), 3.39-3.40 (m, 1H),
3.23-3.26 (m, 1H), 2.46 (s, 3H), 2.18-2.20 (m, 2H), 1.29-1.44 (m, 6H); 13C-NMR (100
MHz, CDCl3): δ 149.2, 147.8, 143.5, 137.6, 129.7, 127.1, 122.1, 54.5, 47.6, 31.3, 30.4,
23.6, 22.7, 21.5; IR (Neat) 3058, 2934, 2858, 1580, 1449, 1326, 1157, 1093, 813, 571,
594; HRMS(MALDI): calcd. for [M+Na]+ (C18H22N2S2O2) requires 385.1020, found
385.1020.
4.3.14. 4-Methyl-N-((1R,2R)-2-(naphthalen-1-ylthio)cyclohexyl)benzenesulfonamide
(4n)
Yield: 90%; white solid. m.p. = 88-91oC. Enantiomeric excess: 54%, [α]D27 = -23.0 (c
= 1.8, CHCl3), determined by HPLC (Chiralpak AD-H column, hexane/i-PrOH 85:15,
flow rate 1.0 ml/min, tminor = 14.1 min, tmajor = 10.8 min, λ = 254 nm); 1H-NMR (400
MHz, CDCl3): δ 8.39 (d, J = 8.0 Hz, 1H), 7.88-7.90 (m, 1H), 7.83 (d, J = 8.0 Hz, 1H),
7.73 (d, J = 8.0 Hz, 2H), 7.53-7.60 (m, 3H), 7.40 (t, J = 7.8 Hz, 1H), 7.24 (d, J = 8.0
Hz, 2H), 5.29 (d, J = 4.4 Hz, 1H), 3.04-3.21 (m, 2H), 2.43 (s, 3H), 2.30-2.32 (m, 1H),
13
1.95-1.98 (m, 1H), 1.29-1.44 (m, 6H); C-NMR (100 MHz, CDCl3): δ 143.3, 137.4,
134.4, 134.1, 132.4, 130.8, 129.6, 128.8, 128.6, 127.3, 126.7, 126.3, 125.6, 125.5,
55.5, 51.5, 32.2, 31.4, 24.2, 23.2, 21.6; IR (Neat) 3276, 2934, 2857, 1628, 1254, 1157;
HRMS(MALDI): calcd. for [M+H]+ (C23H26NS2O2) requires 412.1394, found
412.1399.
4.3.15. 4-Methyl-N-((1R,2R)-2-(naphthalen-2-ylthio)cyclohexyl)benzenesulfonamide
(4o)17
28
Yield: 91%; white solid. Enantiomeric excess: 57%, [α]D = 19.4 (c = 1.85, CHCl3),
determined by HPLC (Chiralpak AD-H column, hexane/i-PrOH 4:1, flow rate 1.0

ACCEPTED MANUSCRIPT
ml/min, tminor = 13.1 min, tmajor = 10.1 min, λ = 254 nm); 1H-NMR (400 MHz, CDCl3):
δ 7.74-7.86 (m, 6H), 7.51-7.53 (m, 2H), 7.37-7.39 (m, 1H), 7.22 (d, J = 7.8 Hz, 2H),
5.42-5.43 (m, 1H), 3.10-3.14 (m, 2H), 2.41 (s, 3H), 2.29-2.31 (m, 1H), 2.09-2.12 (m,
1H), 1.60-1.62 (m, 2H), 1.31-1.33 (m, 4H); MS (ESI): m/z 434.1 (M++Na).
4.3.16. 4-Methyl-N-((1R,2R)-2-(phenylthio)cyclopentyl)benzenesulfonamide (4p)17
26
Yield: 95%; white solid. Enantiomeric excess: 51%, [α]D = 11.2 (c = 1.6, CHCl3),
determined by HPLC (Chiralpak AD-H column, hexane/i-PrOH 95:5, flow rate 1.0
ml/min, tminor = 29.7 min, tmajor = 32.5 min, λ = 254 nm); 1H-NMR (400 MHz, CDCl3):
δ 7.59 (d, J = 8.0 Hz, 2H), 7.17-7.20 (m, 7H), 4.71 (d, J = 4.0 Hz, 1H), 3.21-3.27 (m,
2H), 2.36 (s, 3H), 2.00-2.01 (m, 2H), 1.58-1.65 (m, 2H), 1.39-1.54 (m, 2H); MS (ESI):
m/z 370.1 (M++Na).
4.3.17. N-((1S,2S)-2-((4-Chlorophenyl)thio)cyclohexyl)-3,5-dinitrobenzamide (4q)
Yield: 99%; yellow solid. m.p. = 191-192oC. Enantiomeric excess: 62%, [α]D22 = 33.2
(c = 0.83, CHCl3), determined by HPLC (Chiralpak AD-H column hexane/i-PrOH 9:1,
flow rate 1.0 ml/min, tminor = 18.2 min, tmajor = 14.2 min, λ = 254 nm); 1H-NMR (400
MHz, CDCl3): δ 9.05-9.07 (m, 1H), 8.68 (d, J = 1.6 Hz, 2H), 7.33-7.35 (m, 2H),
7.07-7.18 (m, 3H), 6.19 (d, J = 6.8 Hz, 1H), 3.94-3.96 (m, 1H), 3.07 (td, J = 3.6 Hz, J
13
= 7.6 Hz, 1H), 2.14-2.24 (m, 2H), 1.72-1.75 (m, 2H), 1.28-1.46 (m, 4H); C-NMR
(100 MHz, CDCl3): δ 162.0, 148.5, 137.9, 134.2, 132.1, 129.2, 127.1, 121.0, 68.0,
54.8, 53.5, 51.7, 33.6, 32.9, 29.7, 25.9, 25.6, 24.6; IR (Neat) 3306, 3096, 2937, 1644,
1541, 1476, 1343, 1095, 1013, 918, 821, 730; HRMS(MALDI): calcd. for [M+H]+
(C23H26NS2O2) requires 412.1394, found 412.1399; HRMS(MALDI): calcd. for
[M+H]+ (C19H19N3ClSO5) requires 436.0722, found 436.0728.
4.3.18. (4aR,10aR)-10-Tosyl-2,3,4,4a,10,10a-hexahydro-1H-phenothiazine(5)18
25
Yield: 70%; yellow oil. Enantiomeric excess: 61%, [α]D = -22.8 (c = 1.7, CH2Cl2),
determined by HPLC (Phenomenex Cellulose-2 column, hexane/i-PrOH 85:15, flow
rate 1.0 ml/min, tminor = 6.98 min, tmajor = 6.22 min, λ = 254 nm); 1H-NMR (400 MHz,
CDCl3): δ 7.59 (d, J = 8.0 Hz, 2H), 7.17-7.20 (m, 7H), 4.71 (d, J = 4.0 Hz, 1H),
3.21-3.27 (m, 2H), 2.36 (s, 3H), 2.00-2.01 (m, 2H), 1.58-1.65 (m, 2H), 1.39-1.54 (m,
2H); MS (ESI): m/z 382.2 (M++Na).
Acknowledgements
This project is financially supported by National Basic Research Program of China
(973 Program, 2010CB833204), National Natural Science Foundation of China for
financial support (No. 21290184, 21272247, 21172001, 21372008).
Supplementary data
Supplementary data associated with this article can be found in the online version at
doi:
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Electronic Supplementary Information
Enantioselective desymmetrization of meso-aziridines with
benzenethiols catalyzed by chiral bifunctional quaternary
phosphonium salts
Jiaxing Zhang,a Dongdong Cao,b Hongyu Wang,b Gang Zhao,b* and
Yongjia Shanga*
Contents
Electronic Supplementary Information ........................................................................................1
1. Optimization of reaction conditions with catalyst 1f (TableS1, Table S2)....................................2
2. NMR spectra copies for catalysts (1f-1l) and some products .......................................................3
3. HPLC spectra for compounds.....................................................................................................15

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1. Optimization of reaction conditions with catalyst 1f
(TableS1, Table S2)
Table S1 Screening of solventsa
Entry
Solvent
CCl4
CHCl2CH2Cl
1,2-dichlorobenzene
p-xylene
PhCF3
Time (h)
Eeb(%)
41
3
16
25
21
11
4
14
-10
-
1
2
3
4
5
6
7
8
9
4
4
4
4
4
mesitylene
CH3CN
MTBE
4
12
12
12
12
THF
EtOH
10
a Reactions were carried out using (0.1 mmol) of 2a, (0.15 mmol) 3a, 5 mol% of 1f, 0.2 mmol of
K2HPO4. b Determined by chiral stationary phase HPLC.
Table S2 Screening of basesa
Entry
Base
PhCOONa
DABCO
DBU
DIPEA
DMAP
KF
Time (h)
Yieldb (%)
Eec(%)
47
1
2
3
4
5
6
7
8
9
4
4
4
4
4
4
4
4
4
99
99
99
99
99
99
99
99
90
99
99
37
0
19
27
43(59d)
27
CsF
CH3COOK
PhCOOK
Et3N
34
48(57d)
48(32d)
10
11
4
12
KHCO3
56d
a Reactions were carried out using (0.1 mmol) of 2a, (0.15 mmol) 3a, 5 mol% of 1f. Isolated
b
yields. c Determined by chiral stationary phase HPLC. d Reaction at 0oC.

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2. NMR spectra copies for catalysts (1f-1l) and some
products

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