Chiral squaramide-catalysed one-pot enantioselective sulfa-Michael addition/thioesterification of thiols with α,β-unsaturated N-acylated succinimides

Article abstract of DOI:10.1039/c3ob42137f

A novel highly enantioselective one-pot dithiolation through sulfa-Michael addition/thioesterification of thiols with α,β-unsaturated N-acylated succinimides catalysed by squaramide has been developed. This organocatalysed reaction proceeded well in high to excellent yields (up to >99%) to afford useful bioactive β-sulfated thioester derivatives with high enantioselectivities (up to 96% ee). This journal is The Royal Society of Chemistry 2014.

Full text of DOI:10.1039/c3ob42137f

Organic &
Biomolecular Chemistry
View Article Online
View Journal | View Issue
PAPER
Chiral squaramide-catalysed one-pot
enantioselective sulfa-Michael addition/
thioesterification of thiols with α,β-unsaturated
N-acylated succinimides†
Cite this: Org. Biomol. Chem., 2014,
12, 1585
Bo-Liang Zhao and Da-Ming Du*
Received 28th October 2013,
Accepted 27th November 2013
A novel highly enantioselective one-pot dithiolation through sulfa-Michael addition/thioesterification of
thiols with α,β-unsaturated N-acylated succinimides catalysed by squaramide has been developed. This
organocatalysed reaction proceeded well in high to excellent yields (up to >99%) to afford useful bioactive
β-sulfated thioester derivatives with high enantioselectivities (up to 96% ee).
DOI: 10.1039/c3ob42137f
www.rsc.org/obc
α,β-unsaturated N-acylated succinimides have not yet been
achieved.
Introduction
To develop a mild and efficient method for carbon–sulfur
In recent years, chiral squaramide catalysts have been used
(C–S) bond formation without the use of transition metal catalysts in various organic reactions.7 Chen and coworkers have
is still a major challenge.1 Optically active chiral thiols and sul- reported sulfa-Michael addition of various thiols to trans-chal-
fides seen as having broad prospects of application in biology cones and α,β-unsaturated N-acylated oxazolidinones using
are a class of compounds with potential pharmaceutical squaramide as a catalyst and the corresponding products were
value.2 Especially, the synthesis of enantiomerically pure β-sul- obtained in high yields with enantioselectivity.6a,g Herein, we
fated carboxylic acid derivatives has become an important part report a novel highly enantioselective one-pot dithiolation
of organic synthesis.3 As substructures, they exist in pharma- through sulfa-Michael addition/thioesterification of thiols
ceuticals and various biologically active compounds.4 There- with α,β-unsaturated N-acylated succinimides catalysed by
fore, the development of a simple and efficient catalytic squaramide. This organocatalysed reaction proceeded well in
asymmetric sulfa-Michael reaction has seen considerable high to excellent yields (up to >99%) to afford β-sulfated thio-
research effort invested and is currently a hot topic. However, ester derivatives with high enantioselectivities (up to 96% ee).
the development of effective catalysts for asymmetric sulfa-
Michael reactions involving the less reactive but synthetically
more useful simple alkyl thiols remains a significant chal-
Results and discussion
lenge. Several effective chiral metallic5 and organic catalysts6
have been developed for conjugate additions of aryl thiols to
various Michael acceptors. Therefore, the development of an
efficient catalytic system suitable for sulfa-Michael additions
of aryl and alkyl thiols to α,β-unsaturated acid derivatives
becomes particularly important. In recent years, there have
been a few examples of sulfa-Michael addition of both alkyl
and aryl thiols to α,β-unsaturated N-acylated oxazolidinones
and α,β-unsaturated N-acylated 3,5-dimethyl-1H-pyrazole. In
contrast, as a Michael acceptor, the analogous compounds of
Initially, we made a trial through the reaction (E)-1-(but-2-
enoyl)-pyrrolidine-2,5-dione 1a with thiophenol 2a using cata-
lyst I. The experimental results show that 1a may undergo an
activation process by the squaramide moiety through a double
hydrogen-bonding interaction in a manner similar to α,β-un-
saturated N-acylated oxazolidinones. At first, we obtained the
single sulfa-Michael addition product. As the reaction pro-
ceeded, the product of single sulfa-Michael addition slowly
disappeared and completely converted into the desired
product 3aa, which can be tracked by TLC. No matter how the
ratio of the two reactants was adjusted, there was always some
3aa product formed. This means that we can not obtain a high
yield of the single sulfa-Michael addition compound. In order
to increase the yield of this reaction and control the reaction,
we choose to extend the reaction time and finally obtain the
novel compound 3aa having two sulfur functional groups and
School of Chemical Engineering and Environment, Beijing Institute of Technology,
Beijing 100081, People’s Republic of China. E-mail: dudm@bit.edu.cn;
Tel: +86 10 68914985
†Electronic supplementary information (ESI) available: 1H and 13C NMR spectra
of new compounds, and HPLC chromatograms. See DOI: 10.1039/c3ob42137f
This journal is © The Royal Society of Chemistry 2014
Org. Biomol. Chem., 2014, 12, 1585–1594 | 1585

View Article Online
Paper
Organic & Biomolecular Chemistry
having broad prospect of application in biology. So far, there is
no similar report about the synthesis of this type of chiral
compound.8
We then compared the performance of α,β-unsaturated
N-acylated succinimide 1a, α,β-unsaturated N-acylated phthal-
imide 4, α,β-unsaturated N-acylated saccharin 5 and α,β-unsatu-
rated N-acylated benzotriazole 6 in this cascade Michael
addition/thioesterification with thiophenol 2a using squara-
mide I as catalyst. The results are listed in Table 1. From com-
prehensive consideration of the yield and enantioselectivity of
product 3aa, α,β-unsaturated N-acylated succinimide 1a is the
best Michael acceptor. Notably, we found that the course of
this reaction can be divided into two steps as monitored by
TLC, the first stage is the Michael addition of thiophenol to
α,β-unsaturated amide, the second stage is the thioesterifica-
tion reaction of excess thiophenol replacing the succinimide,
phthalimide, saccharin or benzotriazole. We find the first step
of the reaction which required a few hours for completion is
much faster than the second step which required a few days to
complete. In other words, the reaction rate is controlled by the
second step.
Fig. 1 Screened squaramide and thiourea catalysts.
Table 2 Screening of squaramide catalysts
Based on the above evaluation results, we choose the reac-
tion of (E)-1-(but-2-enoyl)pyrrolidine-2,5-dione 1a with thiophe-
nol 2a as the model reaction. The catalyst screening was firstly
investigated. Some squaramide catalysts and one thiourea cata-
lyst I–X incorporating cinchona alkaloid and (1S,2S)-(+)-1,2-di-
aminocyclohexane were screened (Fig. 1). From Table 2, we can
find that all catalysts could smoothly promote the reaction in
CHCl3 in the presence of 5 mol% catalyst loading at room
temperature for 48–72 h. The squaramide I derived from quini-
dine was identified as the best catalyst to afford the desired
Michael adduct 3aa. Both squaramides I and IV gave good
yields, but the former exhibited better enantioselectivity (81%
ee) (Table 2, entries 1 and 4).
Entrya
Catalyst
Yieldb (%)
eec (%)
1
2
3
4
5
6
7
8
9
I
II
99
99
94
99
95
99
88
86
94
95
81
75
III
IV
V
VI
VII
VIII
IX
X
77d
80
74d
63
70
20d
59
10
33
a Reaction conditions: (E)-1-(but-2-enoyl)pyrrolidine-2,5-dione 1a
(0.2 mmol) and thiophenol 2a (0.48 mmol) in CHCl3 (0.5 mL) with
5 mol% catalyst for 48–72 h at room temperature. b Isolated yields.
c Determined by HPLC on a Daicel Chiralpak OJ-H column. d The
opposite enantiomer.
Table 1 Screening of Michael acceptors
Subsequently, we carried out the screening of the reaction
solvent. The results show that toluene is the optimal solvent
and also confirm that nonpolar solvents without Lewis basic
sites (such as toluene, xylene, dichloromethane, and chloro-
form) are better when used in conjunction with this type of
hydrogen-bonding catalysts. With the optimal catalyst and
solvent in hand, the other parameters, such as temperature
and catalyst loading were further investigated to obtain the
optimal reaction conditions. The results are summarized in
Table 3. Notably, when the model reaction is first performed at
lower temperature for several hours and then warmed to room
temperature, that is to reduce the temperature of the first reac-
tion stage, the enantioselectivity is greatly improved (Table 3,
entries 13 and 14). When increasing the loading of the catalyst,
the enantioselectivity or yield of the product 3aa cannot be
further improved. However, when reducing the loading of the
Entrya
Acceptor
Product
Time (h)
Yieldb (%)
eec (%)
1
2
3
4
1a
4
5
3aa
3aa
3aa
3aa
48
120
96
99
31
20
90
81
91
92
79
6
24
a Reaction conditions: 1a, 4a, 5a or 6a (0.2 mmol) and thiophenol 2a
(0.48 mmol) in CHCl3 (0.5 mL) with 5 mol% catalyst at room
temperature. b Isolated yields. c Determined by HPLC on a Daicel
Chiralpak OJ-H column.
1586 | Org. Biomol. Chem., 2014, 12, 1585–1594
This journal is © The Royal Society of Chemistry 2014

View Article Online
Organic & Biomolecular Chemistry
Paper
Table 3 Optimization of reaction conditions for the asymmetric Michael addition
Entrya
Solvent
Loading
T (°C)
t/h
Yieldb (%)
eec (%)
1
2
3
4
5
6
7
8
CHCl3
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
10
2.5
1
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
36
36
36
36
36
36
36
36
36
36
36
36
1 + 36
2 + 36
2 + 18
2 + 36
3 + 48
6 + 60
99
99
98
75
95
99
90
99
95
94
71
90
99
96
90
96
72
57
81
81
80
76
80
82
82
78
63
80
81
58
86
96
86
94
95
95
CH2Cl2
CH2ClCH2Cl
CCl4
THF
PhMe
Xylene
α,α,α-Trifluorotoluene
CHCN
Et2O
1,4-Dioxane
H2O
PhMe
PhMe
PhMe
PhMe
PhMe
PhMe
9
10
11
12
13
14
15
16
17
18
−20 to rt
−78 to rt
−78 to 60
−78 to rt
−78 to rt
−78 to rt
a Reaction conditions: (E)-1-(but-2-enoyl)pyrrolidine-2,5-dione 1a (0.2 mmol) and thiophenol 2a (0.48 mmol) in solvent of 0.5 mL. b Isolated
yields. c Determined by HPLC on a Daicel Chiralpak OJ-H column.
catalyst, the yield of product sharply decreased. This phenom- 96% ee) can be obtained when various aryl or alkyl thiols were
enon may be due to the second thioesterification stage that used as the nucleophiles. It is noteworthy that the enantio-
needs a strong catalytic environment to react completely selectivity will decrease with the increase of steric hindrance of
(Table 3, entries 17 and 18).
the substituent on the aromatic ring of the thiol (Table 4,
Having identified the optimized conditions for this reac- entry 3). The electronic nature of the 4-substituted group on the
tion, a variety of thiols was then tested using 1a as a Michael aromatic ring of thiols has little effect on the enantioselectivity
acceptor (Table 4). Good to high enantioselectivities (up to (Table 4, entries 2, 4, 5 and 6). A longer reaction time was
required for the completion of the reaction when less reactive
benzyl mercaptan was employed as the nucleophile, and the
corresponding enantioselectivity also decreased. We have tried
to improve the enantioselectivities of products 3ah–3ai by
Table 4 sulfa-Michael addition/thioesterification of thiols to (E)-1-
(but-2-enoyl)pyrrolidine-2,5-dione 1a
increasing the loading of catalyst or adjusting the temperature,
but the outcome cannot be improved (Table 4, entries 8
and 9).
To extend the scope of this reaction, sulfa-Michael
addition/thioesterification with structurally different substi-
Entrya
R
Product
t/h
Yieldb (%)
eec (%)
tuted N-acryl succinimides 1b–1m were investigated. The
results are summarized in Table 5. Good to high enantio-
selectivities were achieved for a wide variety of Michael donors
and acceptors. We find that as the alkyl chain grows and the
steric hindrance increases at the β-substituted position of 1,
the enantioselectivity and yield moderately decrease. When the
β-substituted position of 1 was replaced by aryl substituents,
the rate of sulfa-Michael addition reduces. But in contrast, the
thioesterification reaction rate and the yields of product 3 has
1
2
3
4
5
6
7
8
9
C6H5
3aa
3ab
3ac
3ad
3ae
3af
3ag
3ah
3ai
2 + 48
2 + 48
2 + 48
2 + 48
2 + 48
2 + 48
2 + 48
6 + 72
6 + 72
96
95
94
95
95
97
94
89
91
96
95
71
93
91
93
94
48
47
4-MeC6H4
2-MeOC6H4
4-ClC6H4
4-BrC6H4
4-FC6H4
2-Naphthyl
Bn
4-ClBn
a Reaction conditions: (E)-1-(but-2-enoyl)pyrrolidine-2,5-dione 1a significantly increased (Table 5, entries 4–6). Next, we evalu-
(0.2 mmol) and thiophenol 2a (0.48 mmol) in toluene (0.5 mL) with
ated the reaction of benzyl mercaptan with the Michael accep-
tors 1 containing aryl substituents. We were pleased to find
that similar results to those described above take place, and
5 mol% catalyst at −78 °C for a few hours, and then the reaction was
allowed to warm to room temperature. b Isolated yields. c Determined
by HPLC on a Daicel Chiralpak IB or OJ-H column.
This journal is © The Royal Society of Chemistry 2014
Org. Biomol. Chem., 2014, 12, 1585–1594 | 1587

View Article Online
Paper
Organic & Biomolecular Chemistry
Table 5 Substrate scope of sulfa-Michael addition/thioesterification of
thiols to α,β-unsaturated N-acylated succinimides
Yieldb eec
Entrya R1
R2
Product t/h (%)
(%)
1d
2d
3e
4
Et (1b)
n-Pr (1c)
i-Pr (1d)
C6H5 (1e)
C6H5 (1e)
C6H5 (1e)
C6H5 (1e)
C6H5 (1e)
C6H5 (2a)
C6H5 (2a)
C6H5 (2a)
C6H5 (2a)
C6H5 (2a)
4-MeC6H4 (2b) 3eb
Bn (2h)
Bn (2h)
4-ClBn (2i)
Bn (2h)
4-ClBn (2i)
Bn (2h)
4-ClBn (2i)
Bn (2h)
3ba
3ca
3da
3ea
3ea
60
96
120
18 >99
18 >99
18 >99
30
30
48
48
48
48
48
60
60
60
60
48
48
48
97
93
82
90
68
82
73
70
80
91
89
89
90
90
82
79
90
88
87
86
90
92
89
89
5f
6
7
3eh
3eh
3ei
3fh
3fi
3gh
3gi
3hh
3ih
3jh
3ji
99
95
99
96
94
99
99
99
98
97
99
98
94
99
8g
9
Fig. 2 Proposed reaction mechanism.
C6H5 (1e)
10
11
12
13
14
15
16
17
18
19
20
21
4-ClC6H4 (1f)
4-ClC6H4 (1f)
2-ClC6H4 (1g)
2-ClC6H4 (1g)
4-BrC6H4 (1h)
4-FC6H4 (1i)
4-MeOC6H4 (1j) Bn (2h)
4-MeOC6H4 (1j) 4-ClBn (2i)
1-Naphthyl (1k) Bn (2h)
1-Naphthyl (1k) 4-ClBn (2i)
4-O2NC6H4 (1l) Bn (2h)
4-MeC6H4 (1m) Bn (2h)
enantiomer. Then, the excess thiophenol continues to be
activated by the tertiary nitrogen of the quinuclidine and
formation of the new anion. The final step is thioesterification
of transient ion pair C with the removal of the succinimide
auxiliary giving bifunctional product 3aa.
Bn (2h)
3kh
3ki
3lh
3mh
Conclusions
48 >99
a Reaction conditions: 1 (0.2 mmol) and 2 (0.48 mmol) in 0.5 mL of
toluene with 5 mol% catalyst I at room temperature. b Isolated yields.
c Determined by HPLC. d The reaction firstly performed at −78 °C for
2 h, and then allowed to warm to room temperature. e The reaction
firstly performed at −78 °C for 4 h, and then allowed to warm to room
temperature. f The reaction firstly performed at −78 °C for 10 h, and
then allowed to warm to room temperature. g The reaction firstly
performed at −40 °C for 12 h, and then allowed to warm to room
temperature.
In conclusion, we have developed an effective one-pot enantio-
selective sulfa-Michael addition/thioesterification of thiols
with α,β-unsaturated N-acylated succinimides using squara-
mide as catalyst, the corresponding disulfur products with
good to excellent yields (up to >99%) and high enantio-
selectivities (up to 96% ee) were obtained. This reaction pro-
vides a facile and innovative access to β-sulfated thioester
derivatives from α,β-unsaturated N-acylated succinimides. A broad
scope of substrates and easily available raw materials make this
approach very competitive in the synthesis of enantiomerically
pure β-sulfated thioester derivatives. Further studies focusing on
the development of new applications of squaramide catalysts in
Michael additions are currently under way in our laboratory.
the final corresponding enantioselectivities of products 3 have
been significantly improved, which should be ascribed to the
decrease of relative reactivity of benzyl mercaptans (Table 5,
entries 7–9). This phenomenon may be ascribed to increasing
probability of the good Michael addition control of the process
by the chiral catalyst. However, the position of the substituent
on the aromatic ring of Michael acceptor has an evident effect
on enantioselectivity (Table 5, entries 10–13). The electronic
nature of the substituent on the aromatic ring of the Michael
Experimental
General information
acceptor or donor has little effect on enantioselectivity of the Unless otherwise stated, commercially available compounds
product (Table 4, entries 14–21).
were used without further purification. Column chromato-
The proposed transition state models to explain the gene- graphy was carried out with silica gel (200–300 mesh). Melting
ration of the final product 3aa are shown in Fig. 2. Squaramide points were measured with a melting point apparatus without
activates the (E)-1-(but-2-enoyl)pyrrolidine-2,5-dione through a correction. 1H NMR spectra were recorded with a Varian
double hydrogen-bonding interaction, while the thiophenol is Mercury-plus 400 MHz spectrometer. Chemical shifts were
activated by the tertiary nitrogen of the quinuclidine. Initially reported in ppm with the internal TMS signal at 0.0 ppm as a
the thiophenol anion attack the (E)-1-(but-2-enoyl)pyrrolidine- standard. The data are reported as follows: chemical shift
2,5-dione from the Si-face via transition state A forming the (ppm), and multiplicity (s = singlet, d = doublet, t = triplet, q =
corresponding Michael adduct anion, subsequently the gener- quartet, m = multiplet or unresolved, br s = broad singlet),
ated anion abstract the proton from the quinuclidine nitrogen coupling constant(s) in Hz, integration assignment. 13C NMR
via transition state B leads to the formation of the major spectra were recorded at 100 MHz. Infrared spectra were
1588 | Org. Biomol. Chem., 2014, 12, 1585–1594
This journal is © The Royal Society of Chemistry 2014

View Article Online
Organic & Biomolecular Chemistry
Paper
obtained with a Perkin Elmer Spectrum One spectrometer. General procedure for one-pot enantioselective sulfa-Michael
The high resolution MS spectra were obtained with ESI ioniza- addition/thioesterification
tion using a Bruker APEX IV FTMS spectrometer. Optical
A
mixture of α,β-unsaturated N-acylated succinimide 1
rotations were measured with a WZZ-3 polarimeter at the indi-
cated concentration with unit g per 100 mL. The enantiomeric
excesses were determined by chiral HPLC using an Agilent
1200 LC instrument with Daicel Chiralpak column IA, IB, OJ-H
or AD-H.
(0.2 mmol) and catalyst VII (6.3 mg, 0.01 mmol, 5 mol%) was
stirred at room temperature or low temperature for 15 min,
then thiol 2 (0.48 mmol) was added in one portion. After stir-
ring at room temperature or first reacting under low tempera-
ture conditions for a few hours, and then allowing to warm to
room temperature for 18–120 h, the reaction mixture was con-
centrated and directly purified by silica gel column chromato-
graphy to afford the desired product 3.
Synthesis of organocatalysts
Squaramide catalysts I–V,7c IX and X,7d VII,9 thiourea VI10 were
prepared according to the reported procedures.
(S)-3-Phenylsulfanylthiobutyric
acid
S-phenyl
ester
(3aa).8 The title compound 3aa was obtained according to the
general procedure as yellow oil (55.4 mg, 96% yield). HPLC
(Daicel Chiralpak OJ-H, n-hexane–2-propanol = 70 : 30, flow
Squaramide VIII
rate 1.0 mL min−1, detection at 254 nm): retention time: tmajor
=
16.9 min, tminor = 49.9 min, 96% ee. [α]2D5 +45.9 (c 2.23,
CH2Cl2); 1H NMR (400 MHz, CDCl3): δ 7.46–7.43 (m, 3H, ArH),
7.41–7.37 (m, 4H, ArH), 7.34–7.24 (m, 3H, ArH), 3.76–3.67 (m,
1H, CH), 2.98 (dd, J1 = 15.2 Hz, J2 = 5.2 Hz, 1H, CH2), 2.75 (dd,
J1 = 15.2 Hz, J2 = 8.8 Hz, 1H, CH2), 1.36 (d, J = 6.8 Hz, 3H, CH3)
ppm; 13C NMR (100 MHz, CDCl3): δ 195.3, 134.4, 133.6, 132.7,
129.5, 129.2, 129.0, 127.5, 127.4, 50.3, 39.6, 20.5 ppm.
(S)-3-p-Tolylsulfanylthiobutyric acid S-p-tolyl ester (3ab).8 The
title compound 3ab was obtained according to the general
procedure as yellow oil (61.4 mg, 95% yield). HPLC (Daicel
In 25 mL round-bottomed flask, 1-amino-2,3,4,6-tetraacetyl-
β-D-glucopyranose11 (1.74 g, 5.0 mmol) was added to dimethyl
squarate (0.71 g, 5.0 mmol) which was dissolved in 10 mL
methanol at room temperature. The reaction mixture was
stirred for 48 h at room temperature and a large white precipi-
tate was obtained by filtration to afford the mono-squaramide
as a white solid (1.65 g, 72% yield). To a solution of 9-amino-
(9-deoxy)epihydroquinine10 (325 mg, 1.0 mmol) in CH2Cl2
(10 mL) was added mono-squaramide (457 mg, 1 mmol). After
stirring for 72 h at room temperature, the squaramide catalyst
VIII was obtained by filtration as a white solid (419 mg, 56%
Chiralpak OJ-H, n-hexane–2-propanol
= 70 : 30, flow rate
1.0 mL min−1, detection at 254 nm): retention time: tmajor
=
10.5 min, tminor = 25.1 min, 95% ee. [α]2D5 +45.6 (c 3.07,
1
CH2Cl2); H NMR (400 MHz, CDCl3): δ 7.35 (d, J = 8.0 Hz, 2H,
ArH), 7.26–7.19 (m, 4H, ArH), 7.12 (d, J = 8.0 Hz, 2H, ArH),
3.65–3.60 (m, 1H, CH), 2.93 (dd, J1 = 15.2 Hz, J2 = 5.6 Hz, 1H,
CH2), 2.71 (dd, J1 = 15.4 Hz, J2 = 9.2 Hz, 1H, CH2), 2.36 (s, 3H,
CH3), 2.34 (s, 3H, CH3), 1.33 (d, J = 6.8 Hz, 3H, CH3) ppm;
13C NMR (100 MHz, CDCl3): δ 195.9, 139.7, 137.8, 134.3, 133.5,
130.0, 129.7, 123.9, 50.2, 40.0, 21.3, 21.1, 20.5 ppm.
1
yield). M.p. 182–184 °C; [α]2D8 = −43.3 (c 0.30, DMSO). H NMR
(400 MHz, CDCl3): δ 8.63 (s, 1H, ArH), 8.03 (d, J = 9.2 Hz, 1H,
ArH), 7.75 (s, 1H, ArH), 7.47 (d, J = 4.4 Hz, 1H, ArH), 7.41 (d,
J = 9.2 Hz, 1H, ArH), 6.16 (br s, 1H, CH), 5.43 (d, J = 7.6 Hz,
1H, CH), 5.29 (t, J = 9.2 Hz, 1H, CH), 5.04 (t, J = 9.6 Hz, 1H,
CH), 4.96 (s, 1H, CH), 4.28 (dd, J1 = 12.0 Hz, J2 = 4.4 Hz, 1H,
CH), 4.03 (d, J = 6.0 Hz, 1H, CH2), 3.98 (s, 3H, OCH3), 3.90 (d,
J = 9.6 Hz, 1H, CH2), 3.47 (br s, 2H, CH2), 3.27 (t, J = 10.4 Hz,
1H, CH), 2.78 (br s, 1H, CH), 2.50 (d, J = 10.4 Hz, 1H, CH), 2.05
(s, 3H, COCH3), 2.02 (s, 3H, COCH3), 2.00 (s, 3H, COCH3), 1.97
(s, 3H, COCH3), 1.68 (s, 2H, CH2), 1.60–1.41 (m, 5H, CH2),
1.34–1.24 (m, 3H, CH2), 0.83 (t, J = 7.2 Hz, 3H, CH3) ppm;
13C NMR (100 MHz, CDCl3): δ 184.6, 182.6, 170.5, 169.7, 169.5,
168.4, 158.5, 147.5, 144.7, 131.8, 131.7, 122.4, 122.3, 119.3,
109.7, 101.5, 81.9, 77.2, 73.3, 73.0, 70.8, 67.9, 61.6, 60.0, 57.3,
55.9, 40.8, 36.7, 27.8, 27.2, 25.5, 24.8, 20.8, 20.6, 20.5,
11.9 ppm; IR (KBr): ν 3194, 3169, 3030, 2940, 2866, 1800, 1751,
1688, 1680, 1652, 1622, 1587, 1571, 1543, 1511, 1473, 1461,
1435, 1368, 1322, 1230, 1170, 1140, 1093, 1036, 976, 909, 850,
(S)-3-(2-Methoxyphenylsulfanyl)thiobutyric acid S-(2-methoxy-
phenyl)ester (3ac). The title compound 3ac was obtained
according to the general procedure as yellow oil (65.5 mg, 94%
yield). HPLC (Daicel Chiralpak OJ-H, n-hexane–2-propanol =
70 : 30, flow rate 1.0 mL min−1, detection at 254 nm): retention
time: tmajor = 19.6 min, tminor = 32.7 min, 71% ee. [α]2D5 +21.2
(c 3.28, CH2Cl2); 1H NMR (400 MHz, CDCl3): δ 7.41–7.24 (m,
4H, ArH), 6.99–6.87 (m, 4H, ArH), 3.88 (s, 3H, CH3), 3.87–3.84
(m, 1H, CH), 3.81 (s, 3H, CH3), 2.96 (dd, J1 = 15.2 Hz, J2
=
4.4 Hz, 1H, CH2), 2.73 (dd, J1 = 15.0 Hz, J2 = 9.6 Hz, 1H, CH2),
1.37 (d, J = 7.6 Hz, 3H, CH3) ppm; 13C NMR (100 MHz, CDCl3):
δ 194.9, 159.0, 158.7, 136.5, 133.4, 131.7, 128.9, 121.8, 121.0,
120.9, 115.7, 111.5, 110.8, 55.9, 55.7, 50.2, 37.7, 20.0 ppm;
IR (KBr): ν 3004, 2963, 2935, 2836, 1699, 1582, 1477, 1462,
1432, 1273, 1260, 1245, 1178, 1161, 1105, 1091, 1070, 1041,
1023, 983, 798, 750, 686 cm−1; HRMS (ESI): m/z calcd for
C18H20NaO3S2 [M + Na]+ 371.07461, found 371.07538.
715, 694, 635, 601 cm−1
; HRMS (ESI): m/z calcd for
(S)-3-(4-Chlorophenylsulfanyl)thiobutyric acid S-(4-chloro-
phenyl)ester (3ad).8 The title compound 3ad was obtained
C38H47N4O12 [M + H]+ 751.31850, found 751.31967.
This journal is © The Royal Society of Chemistry 2014
Org. Biomol. Chem., 2014, 12, 1585–1594 | 1589

View Article Online
Paper
Organic & Biomolecular Chemistry
according to the general procedure as yellow oil (67.9 mg, 95% (m, 1H, CH), 3.05 (dd, J1 = 15.4 Hz, J2 = 5.4 Hz, 1H, CH2), 2.83
yield). HPLC (Daicel Chiralpak OJ-H, n-hexane–2-propanol = (dd, J1 = 15.4 Hz, J2 = 8.6 Hz, 1H, CH2), 1.42 (d, J = 6.8 Hz, 3H,
70 : 30, flow rate 1.0 mL min−1, detection at 254 nm): retention CH3) ppm; 13C NMR (100 MHz, CDCl3): δ 195.5, 134.2, 133.6,
time: tmajor = 10.5 min, tminor = 14.8 min, 93% ee. [α]2D5 +50.4 133.4, 133.3, 132.4, 131.3, 131.1, 130.7, 129.8, 128.8, 128.6,
(c 3.40, CH2Cl2); 1H NMR (400 MHz, CDCl3): δ 7.38 (dd, J1 = 8.6 127.9, 127.72, 127.66, 127.4, 127.1, 126.54, 126.52, 126.3,
Hz, J2 = 2.0 Hz, 4H, ArH), 7.29 (dd, J1 = 8.6 Hz, J2 = 2.4 Hz, 4H, 124.6, 53.4, 50.4, 39.6, 20.6 ppm; IR (KBr): ν 3054, 2965, 2924,
ArH), 3.71–3.62 (m, 1H, CH), 2.93 (dd, J1 = 7.6 Hz, J2 = 5.6 Hz, 2867, 1702, 1625, 1587, 1500, 1454, 1406, 1377, 1343, 1292,
1H, CH2), 2.76 (dd, J1 = 15.4 Hz, J2 = 8.4 Hz, 1H, CH2), 1.35 (d, 1268, 1238, 1195, 1113, 1110, 1074, 1027, 987, 944, 893, 857,
J = 6.8 Hz, 3H, CH3) ppm; 13C NMR (100 MHz, CDCl3): δ 194.7, 813, 745, 665, 631, 473 cm−1; HRMS (ESI): m/z calcd for
136.0, 135.6, 134.2, 133.8, 132.0, 129.5, 129.2, 125.7, 109.7, C24H20NaOS2 [M + Na]+ 411.08478, found 411.08475.
50.2, 40.0, 20.6 ppm.
(S)-S-Benzyl 3-(benzylthio)butanethioate (3ah). The title
(S)-3-(4-Bromophenylsulfanyl)thiobutyric acid S-(4-bromo- compound 3ah was obtained according to the general
phenyl)ester (3ae). The title compound 3ae was obtained procedure as yellow oil (56.3 mg, 89% yield). HPLC (Daicel
according to the general procedure as yellow oil (87.5 mg, 95% Chiralpak OJ-H, n-hexane–2-propanol
= 70 : 30, flow rate
yield). HPLC (Daicel Chiralpak OJ-H, n-hexane–2-propanol = 1.0 mL min−1, detection at 254 nm): retention time: tminor
=
70 : 30, flow rate 1.0 mL min−1, detection at 254 nm): retention 17.9 min, tmajor = 20.8 min, 48% ee. [α]2D5 −5.8 (c 2.82, CH2Cl2);
time: tmajor = 12.2 min, tminor = 16.1 min, 91% ee. [α]D25 +50.5 1H NMR (400 MHz, CDCl3): δ 7.31–7.24 (m, 10H, ArH), 4.13 (s,
(c 4.38, CH2Cl2); 1H NMR (400 MHz, CDCl3): δ 7.53 (d, J = 2H, CH2), 3.74 (s, 2H, CH2), 3.20–3.14 (m, 1H, CH), 2.85 (dd,
8.4 Hz, 2H, ArH), 7.44 (d, J = 8.4 Hz, 2H, ArH), 7.30 (d, J = J1 = 15.2 Hz, J2 = 10.0 Hz, 1H, CH2), 2.66 (dd, J1 = 15.2 Hz, J2 =
8.4 Hz, 2H, ArH), 7.22 (d, J = 8.4 Hz, 2H, ArH), 3.72–3.63 (m, 8.4 Hz, 1H, CH2), 1.27 (d, J = 6.8 Hz, 3H, CH3) ppm; 13C NMR
1H, CH), 2.93 (dd, J1 = 15.4 Hz, J2 = 6.0 Hz, 1H, CH2), 2.76 (dd, (100 MHz, CDCl3): δ 196.5, 138.0, 137.3, 128.80, 128.77, 128.6,
J1 = 15.6 Hz, J2 = 8.0 Hz, 1H, CH2), 1.35 (d, J = 6.8 Hz, 3H, CH3) 128.5, 127.2, 127.0, 50.8, 36.3, 35.5, 33.3, 21.0 ppm; IR (KBr):
ppm; 13C NMR (100 MHz, CDCl3): δ 194.4, 135.8, 135.5, 134.2, ν 3086, 3065, 3026, 2964, 2922, 1683, 1602, 1495, 1453, 1411,
134.1, 132.7, 132.4, 132.1, 129.5, 129.2, 126.3, 124.2, 121.8, 1377, 1261, 1096, 1071, 1025, 800, 701, 661, 564 cm−1; HRMS
50.2, 39.8, 20.6 ppm; IR (KBr): ν 3082, 3056, 2964, 2922, 1705, (ESI): m/z calcd for C18H20NaOS2 [M + Na]+ 339.08478, found
1568, 1472, 1411, 1385, 1340, 1261, 1092, 1067, 1021, 1011, 339.08506.
865, 800, 766, 749, 732, 704 cm−1; HRMS (ESI): m/z calcd for
(S)-S-4-Chlorobenzyl 3-((4-chlorobenzyl)thio)butanethioate
(3ai). The title compound 3ai was obtained according to the
C16H14Br2NaOS2 [M + Na]+ 466.87450, found 466.87485.
(S)-S-(4-Fluorophenyl)3-((4-fluorophenyl)thio)butanethioate general procedure as yellow oil (70.1 mg, 91% yield). HPLC
(3af). The title compound 3af was obtained according to the (Daicel Chiralpak OJ-H, n-hexane–2-propanol = 70 : 30, flow
general procedure as yellow oil (63.0 mg, 97% yield). HPLC rate 1.0 mL min−1, detection at 254 nm): retention time:
(Daicel Chiralpak OJ-H, n-hexane–2-propanol = 70 : 30, flow tminor = 16.6 min, tmajor = 17.9 min, 47% ee. [α]2D5 −6.8 (c 3.51,
rate 1.0 mL min−1, detection at 254 nm): retention time: CH2Cl2); 1H NMR (400 MHz, CDCl3): δ 7.26–7.20 (m, 8H, ArH),
tmajor = 11.5 min, tminor = 21.3 min, 93% ee. [α]2D5 +45.4 (c 3.15, 4.07 (s, 2H, CH2), 3.68 (s, 2H, CH2), 3.16–3.10 (m, 1H, CH),
CH2Cl2); 1H NMR (400 MHz, CDCl3): δ 7.47–7.44 (m, 2H, ArH), 2.82 (dd, J1 = 15.2 Hz, J2 = 6.0 Hz, 1H, CH2), 2.66 (dd, J1
7.37–7.33 (m, 2H, ArH), 7.12–7.08 (m, 2H, ArH), 7.05–7.00 (m, 15.2 Hz, J2 = 8.0 Hz, 1H, CH2), 1.26 (dd, J = 6.4 Hz, 3H, CH3)
2H, ArH), 3.64–3.55 (m, 1H, CH), 2.91 (dd, J1 = 15.4 Hz, J2
ppm; 13C NMR (100 MHz, CDCl3): δ 196.1, 136.4, 136.0, 133.1,
=
=
5.8 Hz, 1H, CH2), 2.74 (dd, J1 = 15.4 Hz, J2 = 8.2 Hz, 1H, CH2), 132.8, 130.1, 128.7, 128.6, 50.7, 36.2, 34.7, 32.6, 21.0 ppm; IR
1.33 (d, J = 6.8 Hz, 3H) ppm; 13C NMR (100 MHz, CDCl3): (KBr): ν 3040, 3028, 2961, 2923, 2863, 1899, 1686, 1596, 1490,
1
1
δ 195.2, 163.5 (d, JC–F = −248.9 Hz), 162.7 (d, JC–F = −247.0 1451, 1406, 1377, 1339, 1277, 1261, 1242, 1197, 1092, 1031,
Hz), 136.4 (d, 3JC–F = 9.0 Hz), 135.8 (d, 3JC–F = 8.0 Hz), 128.2 (d, 1015, 992, 892, 876, 828, 822, 808, 747, 728, 696, 643,
4
2
4JC–F = 3.3 Hz), 122.5 d, JC–F = 3.2 Hz), 116.5 (d, JC–F
=
506 cm−1
; HRMS (ESI): m/z calcd for C18H18Cl2NaOS2
22.0 Hz), 116.1 (d, JC–F = 21.5 Hz), 50.0, 40.5, 20.6 ppm; IR [M + Na]+ 407.00683, found 407.00690.
(KBr): ν 3096, 3069, 2965, 2926, 2869, 1891, 1706, 1590, 1491,
2
(S)-S-Phenyl-3-(phenylthio)pentanethioate (3ba).12 The title
1455, 1398, 1377, 1341, 1291, 1261, 1227, 1157, 1110, 1091, compound 3ba was obtained according to the general
1026, 1014, 989, 897, 881, 829, 815, 793, 764, 659, 646, 636, procedure as yellow oil (58.7 mg, 97% yield). HPLC (Daicel
518 cm−1; HRMS (ESI): m/z calcd for C16H14F2NaOS2 [M + Na]+ Chiralpak OJ-H, n-hexane–2-propanol
=
70 : 30, flow rate
347.03463, found 347.03529.
1.0 mL min−1, detection at 254 nm): retention time: tmajor
=
(S)-S-Naphthalen-2-yl 3-(naphthalen-2-ylthio)butanethioate 13.0 min, tminor = 33.6 min, 90% ee. [α]2D5 +34.2 (c 2.94,
(3ag). The title compound 3ag was obtained according to the CH2Cl2); 1H NMR (400 MHz, CDCl3): δ 7.46–7.37 (m, 7H, ArH),
general procedure as a colorless solid (73.0 mg, 94% yield). 7.35–7.24 (m, 3H, ArH), 3.60–3.53 (m, 1H, CH), 2.94 (dd, J1 =
HPLC (Daicel Chiralpak IB, n-hexane–2-propanol = 95 : 5, flow 15.6 Hz, J2 = 6.4 Hz, 1H, CH2), 2.86 (dd, J1 = 15.6 Hz, J2
=
rate 1.0 mL min−1, detection at 254 nm): retention time: 7.6 Hz, 1H, CH2), 1.76–1.71 (m, 1H, CH2), 1.66–1.59 (m, 1H,
tminor = 9.3 min, tmajor = 16.0 min, 94% ee. M.p. 74–76 °C; CH2), 1.07 (t, J = 7.2 Hz, 3H, CH3) ppm; 13C NMR (100 MHz,
[α]2D5 +103.8 (c 3.65, CH2Cl2); 1H NMR (400 MHz, CDCl3): CDCl3): δ 195.6, 134.4, 133.9, 132.6, 129.5, 129.2, 129.0, 127.4,
δ 7.93–7.75 (m, 8H, ArH), 7.52–7.36 (m, 6H, ArH), 3.91–3.83 127.3, 48.5, 46.6, 27.2, 11.3 ppm.
1590 | Org. Biomol. Chem., 2014, 12, 1585–1594
This journal is © The Royal Society of Chemistry 2014

View Article Online
Organic & Biomolecular Chemistry
Paper
(S)-S-Phenyl-3-(phenylthio)hexanethioate (3ca). The title 133.7, 129.9, 129.6, 128.4, 127.8, 127.5, 49.5, 49.1, 21.3,
compound 3ca was obtained according to the general 21.1 ppm.
procedure as yellow oil (58.9 mg, 93% yield). HPLC (Daicel
Chiralpak OJ-H, n-hexane–2-propanol 70 : 30, flow rate title compound 3eh was obtained according to the general
1.0 mL min−1, detection at 254 nm): retention time: tmajor
procedure as colorless oil (74.9 mg, 99% yield). HPLC (Daicel
8.5 min, tminor = 16.9 min, 68% ee. [α]2D5 +23.8 (c 2.94, CH2Cl2); Chiralpak OJ-H, n-hexane–2-propanol
70 : 30, flow rate
1H NMR (400 MHz, CDCl3): δ 7.45–7.36 (m, 7H, ArH), 1.0 mL min−1, detection at 254 nm): retention time: tminor
7.33–7.23 (m, 3H, ArH), 3.64–3.58 (m, 1H, CH), 2.94 (dd, J1 = 19.4 min, tmajor = 46.7 min, 91% ee. [α]2D5 +115.1 (c 3.74,
15.6 Hz, J2 = 6.0 Hz, 1H, CH2), 2.84 (dd, J1 = 15.8 Hz, J2
CH2Cl2); 1H NMR (400 MHz, CDCl3): δ 7.32–7.13 (m, 15H,
(R)-S-Benzyl-3-(benzylthio)-3-phenylpropanethioate (3eh). The
=
=
=
=
=
8.0 Hz, 1H, CH2), 1.66–1.49 (m, 4H, CH2), 0.92 (t, J = 6.8 Hz, ArH), 4.26–4.21 (m, 1H, CH), 4.03 (s, 2H, CH2), 3.49 (ABq, J =
3H, CH3) ppm; 13C NMR (100 MHz, CDCl3): δ 195.6, 134.4, 13.2 Hz, 2H, CH2), 3.06 (d, J = 8.0 Hz, 2H, CH2) ppm; 13C NMR
133.9, 132.6, 129.4, 129.2, 129.0, 127.4, 127.3, 49.1, 44.8, 36.4, (100 MHz, CDCl3): δ 195.5, 140.4, 137.5, 137.1, 128.9, 128.7,
20.1, 13.8 ppm; IR (KBr): ν 3078, 3059, 2961, 2931, 2872, 1704, 128.54, 128.49, 128.41, 127.9, 127.5, 127.2, 127.0, 49.8, 45.1,
1583, 1478, 1465, 1440, 1410, 1380, 1329, 1300, 1261, 1178, 35.7, 33.2 ppm; IR (KBr): ν 3084, 3061, 3028, 2920, 2851, 1687,
1091, 1068, 1024, 957, 799, 745, 704, 689, 661, 625 cm−1
HRMS (ESI): m/z calcd for C18H20NaOS2 [M + Na]+ 339.08478, 1072, 1048, 1029, 1003, 984, 768, 699, 565 cm−1; HRMS (ESI):
found 339.08564.
m/z calcd for C23H22NaOS2 [M + Na]+ 401.10043, found
(R)-S-Phenyl-4-methyl-3-(phenylthio)pentanethioate (3da). The 401.10036.
;
1615, 1602, 1584, 1494, 1453, 1412, 1320, 1240, 1198, 1181,
title compound 3da was obtained according to the general
(R)-S-4-Chlorobenzyl-3-((4-chlorobenzyl)thio)-3-phenylpropane-
procedure as yellow oil (51.9 mg, 82% yield). HPLC (Daicel thioate (3ei). The title compound 3ei was obtained accord-
Chiralpak OJ-H, n-hexane–2-propanol
=
70 : 30, flow rate ing to the general procedure as yellow oil (88.6 mg, 99% yield).
HPLC (Daicel Chiralpak OJ-H, n-hexane–2-propanol = 70 : 30,
1.0 mL min−1, detection at 254 nm): retention time: tmajor
=
8.9 min, tminor = 23.3 min, 82% ee. [α]2D5 +2.4 (c 2.60, CH2Cl2); flow rate 1.0 mL min−1, detection at 254 nm): retention time:
1H NMR (400 MHz, CDCl3): δ 7.45–7.38 (m, 7H, ArH), tminor = 21.3 min, tmajor = 29.2 min, 89% ee. [α]2D5 +115.4
7.30–7.20 (m, 3H, ArH), 3.67–3.62 (m, 1H, CH), 2.98 (dd, J1 = (c 4.43, CH2Cl2); 1H NMR (400 MHz, CDCl3): δ 7.32–7.19 (m,
15.8 Hz, J2 = 6.4 Hz, 1H, CH2), 2.89 (dd, J1 = 15.8 Hz, J2
=
9H, ArH), 7.09 (d, J = 8.4 Hz, 2H, ArH), 7.06 (d, J = 8.4 Hz, 2H,
7.2 Hz, 1H, CH2), 2.06–2.00 (m, 1H, CH), 1.07 (d, J = 6.8 Hz, ArH), 4.17 (t, J = 7.6 Hz, 1H, CH), 3.98 (ABq, J = 14.4 Hz, 2H,
3H, CH3), 1.03 (d, J = 6.8 Hz, 3H, CH3) ppm; 13C NMR CH2), 3.44 (ABq, J = 13.6 Hz, 2H, CH2), 3.04 (d, J = 7.6 Hz, 2H,
(100 MHz, CDCl3): δ 195.9, 135.3, 134.4, 131.7, 129.4, 129.1, CH2) ppm; 13C NMR (100 MHz, CDCl3): δ 195.2, 140.0, 136.0,
129.0, 127.4, 126.9, 52.2, 46.5, 31.7, 19.8, 18.8 ppm; IR (KBr): 135.8, 133.0, 132.8, 130.2, 130.0, 128.6, 128.5, 127.8, 127.7,
ν 3073, 3059, 2960, 2931, 2872, 1703, 1583, 1478, 1463, 1440, 49.8, 45.2, 35.0, 32.5 ppm; IR (KBr): ν 3077, 3056, 3028, 2922,
1409, 1380, 1328, 1301, 1262, 1178, 1091, 1068, 1024, 959, 797, 2847, 1687, 1597, 1490, 1453, 1406, 1317, 1277, 1258, 1240,
745, 704, 689, 661, 626 cm−1; HRMS (ESI): m/z calcd for 1197, 1178, 1092, 1047, 1028, 1015, 1005, 984, 938, 876, 830,
C18H20NaOS2 [M + Na]+ 339.08478, found 339.08539.
(R)-S-Phenyl-3-phenyl-3-(phenylthio)propanethioate (3ea).8 The for C23H202Cl2NaOS2 [M + Na]+ 469.02248, found 469.02213.
title compound 3ea was obtained according to the general (R)-S-Benzyl-3-(benzylthio)-3-(4-chlorophenyl)propanethioate
824, 806, 763, 749, 699, 642, 506 cm−1; HRMS (ESI): m/z calcd
procedure as a colorless solid (69.4 mg, >99% yield). HPLC (3fh). The title compound 3fh was obtained according to the
(Daicel Chiralpak OJ-H, n-hexane–2-propanol = 70 : 30, flow general procedure as yellow oil (79.3 mg, 96% yield). HPLC
rate 1.0 mL min−1, detection at 254 nm): retention time: (Daicel Chiralpak AD-H, n-hexane–2-propanol = 90 : 10, flow
tminor = 30.4 min, tmajor = 46.6 min, 73% ee. M.p. 75–77 °C; rate 1.0 mL min−1, detection at 254 nm): retention time:
[α]2D5 +43.5 (c 3.47, CH2Cl2); 1H NMR (400 MHz, CDCl3): tminor = 6.8 min, tmajor = 7.6 min, 90% ee. [α]2D5 +117.7 (c 3.96,
δ 7.36–7.30 (m, 6H, ArH), 7.27–7.23 (m, 9H, ArH), 4.73 (t, J = CH2Cl2); 1H NMR (400 MHz, CDCl3): δ 7.29–7.22 (m, 7H, ArH),
8.0 Hz, 1H, CH), 3.25 (d, J = 7.6 Hz, 2H, CH2) ppm; 13C NMR 7.20–7.16 (m, 5H, ArH), 7.11 (d, J = 7.6 Hz, 2H, ArH), 4.17 (dd,
(100 MHz, CDCl3): δ 194.6, 139.8, 134.3, 133.5, 133.1, 129.4, J1 = 6.6 Hz, J2 = 8.6 Hz, 1H, CH), 4.02 (ABq, J = 14.0 Hz, 2H,
129.1, 128.9, 128.5, 127.8, 127.7, 127.6, 127.2, 49.3, 49.1 ppm.
CH2), 3.48 (ABq, J = 13.6 Hz, 2H, CH2), 3.07–2.96 (m, 2H, CH2)
(R)-S-p-Tolyl-3-phenyl-3-(p-tolylthio)propanethioate (3eb).8 The ppm; 13C NMR (100 MHz, CDCl3): δ 195.2, 138.9, 137.2, 137.0,
title compound 3eb was obtained according to the general 133.1, 129.3, 128.8, 128.7, 128.6, 128.50, 128.47, 127.2, 127.1,
procedure as a colorless solid (75.0 mg, >99% yield). HPLC 49.6, 44.4, 35.7, 33.2 ppm; IR (KBr): ν 3085, 3062, 3029, 2960,
(Daicel Chiralpak OJ-H, n-hexane–2-propanol = 70 : 30, flow 2918, 1688, 1615, 1601, 1492, 1453, 1409, 1310, 1291, 1261,
rate 1.0 mL min−1, detection at 254 nm): retention time: 1240, 1197, 1179, 1091, 1072, 1049, 1028, 1014, 988, 942, 814,
tminor = 17.9 min, tmajor = 22.2 min, 80% ee. M.p. 85–87 °C; 765, 701, 529 cm−1; HRMS (ESI): m/z calcd for C23H21ClNaOS2
[α]2D5 +52.4 (c 3.75, CH2Cl2); 1H NMR (400 MHz, CDCl3): [M + Na]+ 435.06146, found 435.06082.
δ 7.30–7.20 (m, 7H, ArH), 7.17–7.12 (m, 4H, ArH), 7.04 (d, J =
(R)-S-4-Chlorobenzyl-3-((4-chlorobenzyl)thio)-3-(4-chlorophenyl)-
7.6 Hz, 2H, ArH), 4.65 (t, J = 7.6 Hz, 1H, CH), 3.22 (d, J = propanethioate (3fi). The title compound 3fi was obtained
7.6 Hz, 2H, CH2), 2.33 (s, 3H, CH3), 2.30 (s, 3H, CH3) ppm; according to the general procedure as yellow oil (90.6 mg, 94%
13C NMR (100 MHz, CDCl3): δ 195.2, 140.0, 139.7, 138.1, 134.3, yield). HPLC (Daicel Chiralpak AD-H, n-hexane–2-propanol =
This journal is © The Royal Society of Chemistry 2014
Org. Biomol. Chem., 2014, 12, 1585–1594 | 1591

View Article Online
Paper
Organic & Biomolecular Chemistry
90 : 10, flow rate 1.0 mL min−1, detection at 254 nm): retention CH2), 3.53 (d, J = 13.2 Hz, 1H, CH2), 3.43 (d, J = 13.6 Hz, 1H,
time: tminor = 10.1 min, tmajor = 11.0 min, 90% ee. [α]2D5 +104.0 CH2), 3.07–2.95 (m, 2H, CH2) ppm; 13C NMR (100 MHz,
(c 4.53, CH2Cl2); 1H NMR (400 MHz, CDCl3): δ 7.27–7.15 (m, CDCl3): δ 195.2, 139.4, 137.2, 137.0, 131.6, 129.6, 128.8, 128.6,
8H, ArH), 7.10–7.04 (m, 4H, ArH), 4.11 (dd, J1 = 7.0 Hz, J2
=
128.5, 128.5, 127.2, 127.1, 121.3, 49.6, 44.4, 35.7, 33.2 ppm; IR
8.6 Hz, 1H, CH), 3.97 (ABq, J = 14.0 Hz, 2H, CH2), 3.49 (d, J = (KBr): ν 3085, 3062, 3028, 2918, 2845, 1687, 1615, 1602, 1588,
13.6 Hz, 1H, CH2), 3.38 (d, J = 13.6 Hz, 1H, CH2), 3.06–2.94 (m, 1495, 1488, 1453, 1405, 1310, 1291, 1240, 1195, 1181, 1103,
2H, CH2) ppm; 13C NMR (100 MHz, CDCl3): δ 194.9, 138.5, 1072, 1049, 1030, 1010, 986, 937, 822, 814, 768, 717, 702, 621,
135.7, 135.7, 133.3, 133.0, 132.9, 130.1, 130.0, 129.2, 128.7, 565, 526 cm−1; HRMS (ESI): m/z calcd for C23H21BrNaOS2
128.6, 49.6, 44.4, 35.0, 32.5 ppm; IR (KBr): ν 3060, 3043, 3028, [M + Na]+ 479.01094, found 479.01182.
2920, 2851, 1689, 1596, 1490, 1408, 1309, 1242, 1197, 1178,
1093, 1049, 1015, 986, 942, 880, 827, 748, 700, 643, 507 cm−1
(R)-S-Benzyl-3-(benzylthio)-3-(4-fluorophenyl)propanethioate
(3ih). The title compound 3ih was obtained according to the
;
HRMS (ESI): m/z calcd for C23H19Cl3NaOS2 [M
+
Na]+ general procedure as a colorless solid (77.7 mg, 98% yield).
502.98351, found 502.98350.
HPLC (Daicel Chiralpak AD-H, n-hexane–2-propanol = 95 : 5,
(R)-S-Benzyl-3-(benzylthio)-3-(2-chlorophenyl)propanethioate flow rate 1.0 mL min−1, detection at 254 nm): retention time:
(3gh). The title compound 3gh was obtained according to the tminor = 8.2 min, tmajor = 8.8 min, 88% ee. M.p. 39–40 °C;
general procedure as yellow oil (81.9 mg, >99% yield). HPLC [α]2D5 +75.7 (c 3.88, CH2Cl2); 1H NMR (400 MHz, CDCl3):
(Daicel Chiralpak AD-H, n-hexane–2-propanol = 98 : 2, flow rate δ 7.29–7.11 (m, 12H, ArH), 6.99–6.94 (m, 2H, ArH), 4.19 (dd,
1.0 mL min−1, detection at 254 nm): retention time: tminor
=
J1 = 6.4 Hz, J2 = 8.8 Hz, 1H, CH), 4.02 (ABq, J = 14.0 Hz, 2H,
11.2 min, tmajor = 12.2 min, 82% ee. [α]2D5 +22.7 (c 4.10, CH2), 3.54 (d, J = 13.2 Hz, 1H, CH2), 3.44 (d, J = 13.2 Hz, 1H,
1
CH2Cl2); H NMR (400 MHz, CDCl3): δ 7.51 (d, J = 7.6 Hz, 1H, CH2), 3.08–2.96 (m, 2H, CH2) ppm; 13C NMR (100 MHz,
1
ArH), 7.32 (d, J = 8.0 Hz, 1H, ArH), 7.25–7.14 (m, 12H, ArH), CDCl3): δ 195.3, 161.9 (d, JC–F = −244.9 Hz), 137.3, 137.1,
3
4.83 (t, J = 7.6 Hz, 1H, CH), 4.07 (s, 2H, CH2), 3.61 (s, 2H, CH2), 136.0, 129.5 (d, JC–F = 8.1 Hz), 128.8, 128.6, 128.5, 128.5,
3.12–3.01 (m, 2H, CH2) ppm; 13C NMR (100 MHz, CDCl3): 127.2, 127.1, 115.4 (d, JC–F = 21.4 Hz), 49.9, 44.4, 35.7,
2
δ 195.1, 138.0, 137.2, 137.1, 133.5, 129.7, 128.9, 128.7, 128.5, 33.2 ppm; IR (KBr): ν 3086, 3063, 3030, 2957, 2921, 2849, 1949,
128.4, 127.2, 127.0, 49.1, 41.8, 36.3, 33.2 ppm; IR (KBr): ν 3086, 1887, 1688, 1682, 1602, 1506, 1497, 1454, 1416, 1311, 1296,
3060, 3026, 2961, 1682, 1602, 1495, 1473, 1452, 1408, 1261, 1260, 1224, 1196, 1181, 1158, 1129, 1097, 1072, 1049, 1028,
1093, 1069, 1031, 800, 751, 725, 696, 594, 562 cm−1; HRMS 1015, 987, 940, 917, 835, 805, 768, 701, 631, 566, 537,
(ESI): m/z calcd for C23H21ClNaOS2 [M + Na]+ 435.06146, found 474 cm−1; HRMS (ESI): m/z calcd for C23H21FNaOS2 [M + Na]+
435.06073.
419.09101, found 419.09080.
(S)-S-4-Chlorobenzyl-3-((4-chlorobenzyl)thio)-3-(2-chlorophenyl)-
(R)-S-Benzyl-3-(benzylthio)-3-(4-methoxyphenyl)propanethioate
propanethioate (3gi). The title compound 3gi was obtained (3jh). The title compound 3jh was obtained according to the
according to the general procedure as yellow oil (95.8 mg, general procedure as yellow oil (79.2 mg, 97% yield). HPLC
>99% yield). HPLC (Daicel Chiralpak OJ-H, n-hexane–2-propa- (Daicel Chiralpak AD-H, n-hexane–2-propanol = 90 : 10, flow
nol = 70 : 30, flow rate 1.0 mL min−1, detection at 254 nm): rate 1.0 mL min−1, detection at 254 nm): retention time:
retention time: tminor = 16.0 min, tmajor = 25.1 min, 79% ee. tminor = 8.5 min, tmajor = 9.3 min, 87% ee. [α]2D5 +88.6 (c 3.96,
1
[α]2D5 +29.2 (c 4.79, CH2Cl2); H NMR (400 MHz, CDCl3): δ 7.48 CH2Cl2); 1H NMR (400 MHz, CDCl3): δ 7.29–7.12 (m, 12H,
(d, J = 7.6 Hz, 1H, ArH), 7.31 (d, J = 7.6 Hz, 1H, ArH), 7.25–7.15 ArH), 6.83 (d, J = 8.4 Hz, 2H, ArH), 4.19 (t, J = 8.0 Hz, 1H, CH),
(m, 6H, ArH), 7.10 (t, J = 8.4 Hz, 4H, ArH), 4.79 (t, J = 7.6 Hz, 4.03 (ABq, J = 14.0 Hz, 2H, CH2), 3.79 (s, 3H, CH3), 3.53 (d, J =
1H, CH), 4.02 (ABq, J = 14.0 Hz, 2H, CH2), 3.55 (s, 2H, CH2), 13.2 Hz, 1H, CH2), 3.44 (d, J = 13.2 Hz, 1H, CH2), 3.07–3.01 (m,
3.09–2.98 (m, 2H, CH2) ppm; 13C NMR (100 MHz, CDCl3): 2H, CH2) ppm; 13C NMR (100 MHz, CDCl3): δ 195.6, 158.8,
δ 194.8, 137.7, 135.83, 135.77, 135.75, 133.5, 133.0, 132.8, 137.6, 137.2, 132.2, 129.0, 128.9, 128.7, 128.5, 128.4, 127.1,
130.2, 130.1, 129.7, 128.9, 128.6, 128.5, 127.2, 49.0, 41.8, 35.6, 127.0, 113.8, 55.2, 50.0, 44.5, 35.6, 33.1 ppm; IR (KBr): ν 3061,
32.5 ppm; IR (KBr): ν 3064, 3030, 2922, 2850, 1899, 1689, 1596, 3029, 3003, 2955, 2932, 2909, 2835, 1688, 1609, 1584, 1511,
1490, 1474, 1441, 1407, 1344, 1306, 1277, 1241, 1196, 1179, 1495, 1453, 1421, 1304, 1283, 1250, 1176, 1110, 1071, 1050,
1128, 1093, 1046, 1035, 1016, 988, 941, 877, 832, 809, 754, 730, 1035, 987, 831, 807, 768, 703, 542 cm−1; HRMS (ESI): m/z calcd
697, 681, 642, 594, 507 cm−1; HRMS (ESI): m/z calcd for for C24H24NaO2S2 [M + Na]+ 431.11099, found 431.11080.
C23H19Cl3NaOS2 [M + Na]+ 502.98351, found 502.98274.
(R)-S-4-Chlorobenzyl-3-((4-chlorobenzyl)thio)-3-(4-methoxy-
(R)-S-Benzyl-3-(benzylthio)-3-(4-bromophenyl)propanethioate phenyl)propanethioate (3ji). The title compound 3ji was
(3hh). The title compound 3hh was obtained according to the obtained according to the general procedure as yellow oil
general procedure as yellow oil (90.6 mg, 99% yield). HPLC (94.5 mg, 99% yield). HPLC (Daicel Chiralpak OJ-H, n-hexane–
(Daicel Chiralpak AD-H, n-hexane–2-propanol = 90 : 10, flow 2-propanol = 70 : 30, flow rate 1.0 mL min−1, detection at
rate 1.0 mL min−1, detection at 254 nm): retention time: 254 nm): retention time: tminor = 39.5 min, tmajor = 55.7 min,
tminor = 7.1 min, tmajor = 8.0 min, 90% ee. [α]D25 +132.2 (c 4.53, 86% ee. [α]2D5 +124.0 (c 4.73, CH2Cl2); 1H NMR (400 MHz,
1
CH2Cl2); H NMR (400 MHz, CDCl3): δ 7.40 (d, J = 8.4 Hz, 1H, CDCl3): δ 7.25–7.14 (m, 6H, ArH), 7.09 (d, J = 8.4 Hz, 2H, ArH),
ArH), 7.29–7.21 (m, 6H, ArH), 7.18–7.10 (m, 6H, ArH), 4.15 (dd, 7.05 (d, J = 8.4 Hz, 2H, ArH), 6.81 (d, J = 8.8 Hz, 2H, ArH), 4.14
J1 = 6.8 Hz, J2 = 8.4 Hz, 1H, CH), 4.01 (ABq, J = 14.0 Hz, 2H, (t, J = 7.6 Hz, 1H, CH), 3.97 (ABq, J = 14.4 Hz, 2H, CH2), 3.80
1592 | Org. Biomol. Chem., 2014, 12, 1585–1594
This journal is © The Royal Society of Chemistry 2014

View Article Online
Organic & Biomolecular Chemistry
Paper
(s, 3H, CH3), 3.47 (d, J = 13.6 Hz, 1H, CH2), 3.38 (d, J = 13.6 Hz, CH2) ppm; 13C NMR (100 MHz, CDCl3): δ 194.8, 148.1, 147.0,
1H, CH2), 3.04–2.98 (m, 2H, CH2) ppm; 13C NMR (100 MHz, 136.9, 136.8, 129.0, 128.8, 128.6, 128.6, 128.5, 127.4, 127.3,
CDCl3): δ 195.3, 158.9, 136.2, 135.9, 132.9, 132.7, 131.7, 130.2, 124.1, 123.7, 49.2, 44.4, 35.9, 33.2 ppm; IR (KBr): ν 3108, 3062,
130.0, 129.0, 128.54, 128.49, 113.8, 55.2, 49.9, 44.6, 34.9, 3029, 2923, 2854, 1684, 1599, 1520, 1495, 1454, 1413, 1346,
32.4 ppm; IR (KBr): ν 3031, 3001, 2955, 2933, 2909, 2836, 1689, 1319, 1242, 1180, 1111, 1072, 1050, 1030, 1014, 986, 856, 769,
1610, 1584, 1511, 1490, 1463, 1441, 1407, 1304, 1282, 1250, 749, 703, 623, 565, 474 cm−1; HRMS (ESI): m/z calcd for
1176, 1110, 1092, 1048, 1036, 1015, 987, 832, 809, 792, 730, C23H21NNaO3S2 [M + Na]+ 446.08551, found 446.08483.
697, 643 cm−1; HRMS (ESI): m/z calcd for C24H22Cl2NaO2S2
(R)-S-Benzyl-3-(benzylthio)-3-(p-tolyl)propanethioate (3mh). The
title compound 3mh was obtained according to the general
[M + Na]+ 499.03305, found 499.03363.
(R)-S-Benzyl-3-(benzylthio)-3-(naphthalen-1-yl)propanethioate procedure as yellow oil (77.8 mg, >99% yield). HPLC (Daicel
(3kh). The title compound 3kh was obtained according to the Chiralpak AD-H, n-hexane–2-propanol = 90 : 10, flow rate
general procedure as yellow oil (84.0 mg, 98% yield). HPLC 1.0 mL min−1, detection at 254 nm): retention time: tminor
=
(Daicel Chiralpak AD-H, n-hexane–2-propanol = 90 : 10, flow 6.2 min, tmajor = 6.7 min, 89% ee. [α]2D5 +110.0 (c 3.88, CH2Cl2);
rate 1.0 mL min−1, detection at 254 nm): retention time: 1H NMR (400 MHz, CDCl3):δ 7.29–7.09 (m, 14H, ArH),
tmajor = 7.3 min, tminor = 9.7 min, 90% ee. [α]2D5 +10.6 (c 4.19, 4.25–4.18 (m, 1H, CH), 4.02 (m, 2H, CH2), 3.49 (ABq, J =
1
CH2Cl2); H NMR (400 MHz, CDCl3): δ 7.84 (d, J = 7.6 Hz, 2H, 13.6 Hz, 2H, CH2), 3.04 (t, J = 1.6 Hz, 2H, CH2), 2.33 (s, 3H,
ArH), 7.75 (d, J = 8.4 Hz, 1H, ArH), 7.63 (br s, 1H, ArH), CH3) ppm; 13C NMR (100 MHz, CDCl3): δ 195.5, 137.6, 137.2,
7.48–7.40 (m, 4H, ArH), 7.24–7.11 (m, 9H, ArH), 5.09 (br s, 1H, 137.2, 137.1, 129.2, 128.9, 128.7, 128.6, 128.4, 128.4, 127.7,
CH), 4.03 (s, 2H, CH2), 3.57 (ABq, J = 13.2 Hz, 2H, CH2), 3.27 127.1, 127.0, 109.6, 49.9, 44.8, 35.6, 33.1, 21.1 ppm; IR (KBr):
(d, J = 7.2 Hz, 2H, CH2) ppm; 13C NMR (100 MHz, CDCl3): ν 3085, 3061, 3028, 2920, 2862, 1688, 1602, 1512, 1495, 1453,
δ 195.9, 137.5, 137.1, 135.8, 133.9, 130.8, 129.0, 128.9, 128.7, 1415, 1317, 1240, 1198, 1182, 1112, 1071, 1050, 1030, 985, 817,
128.5, 128.4, 128.2, 127.2, 127.0, 126.2, 125.7, 125.2, 122.9, 807, 767, 702, 637, 566, 535, 473 cm−1; HRMS (ESI): m/z calcd
49.5, 36.2, 33.2 ppm; IR (KBr): ν 3082, 3061, 3029, 2957, 2919, for C24H24NaOS2 [M + Na]+ 415.11608, found 415.11632.
1686, 1600, 1510, 1495, 1453, 1412, 1396, 1334, 1277, 1240,
1199, 1183, 1158, 1071, 1048, 1028, 1013, 977, 936, 916,
796, 776, 701, 606, 565 cm−1; HRMS (ESI): m/z calcd for
C27H24NaOS2 [M + Na]+ 4451.11608, found 451.11690.
Determination of the absolute configuration of product 3ab
(S)-Methyl-3-(p-tolylthio)butanoate.13
(R)-S-4-Chlorobenzyl-3-((4-chlorobenzyl)thio)-3-(naphthalen-
1-yl)propanethioate (3ki). The title compound 3ki was
obtained according to the general procedure as yellow oil
(93.5 mg, 94% yield). HPLC (Daicel Chiralpak AD-H, n-hexane–
2-propanol = 90 : 10, flow rate 1.0 mL min−1, detection at
254 nm): retention time: tmajor = 11.8 min, tminor = 9.6 min,
92% ee. [α]2D5 +16.0 (c 4.67, CH2Cl2); 1H NMR (400 MHz,
CDCl3): δ 7.80 (dd, J1 = 36.4 Hz, J2 = 7.6 Hz, 3H, ArH), 7.62 (s,
1H, ArH), 7.50–7.40 (m, 3H, ArH), 7.24–7.14 (m, 4H, ArH), 7.01
(d, J = 8.4 Hz, 4H, ArH), 5.05 (s, 1H, CH), 3.97 (ABq, J =
14.0 Hz, 2H, CH2), 3.54 (d, J = 13.2 Hz, 1H, CH2), 3.45 (d, J =
13.6 Hz, 1H, CH2), 3.23 (d, J = 7.2 Hz, 2H, CH2) ppm; 13C NMR
(100 MHz, CDCl3): δ 195.5, 136.0, 135.7, 135.5, 133.9, 132.9,
132.7, 130.7, 130.2, 130.0, 128.9, 128.6, 128.5, 128.3, 126.3,
125.8, 125.2, 125.1, 125.0, 125.0, 122.7, 122.7, 122.6, 49.9, 35.4,
32.5, 28.3 ppm; IR (KBr): ν 3047, 2964, 2927, 1804, 1688, 1613,
1598, 1510, 1490, 1405, 1261, 1166, 1092, 1054, 1015, 979, 861,
797, 776, 734, 704, 641, 605, 507 cm−1; HRMS (ESI): m/z calcd
for C27H22Cl2NaOS2 [M + Na]+ 519.03813, found 519.03989.
(R)-S-Benzyl-3-(benzylthio)-3-(4-nitrophenyl)propanethioate
(3lh). The title compound 3lh was obtained according to the
general procedure as a colorless solid (83.8 mg, 99% yield).
HPLC (Daicel Chiralpak AD-H, n-hexane–2-propanol = 90 : 10,
flow rate 1.0 mL min−1, detection at 254 nm): retention time:
tminor = 13.0 min, tmajor = 17.1 min, 89%. M.p. 61–63 °C;
The title compound was obtained through the reaction of com-
pound 3ab with MeOH under 10 mol% lanthanum(III) trifluoro-
methanesulfonate as yellow oil (41.3 mg, 92% yield).
1
[α]2D5 +26.9 (c 0.72, CH2Cl2); H NMR (400 MHz, CDCl3):δ 7.26
(d, J = 8.0 Hz, 2H, ArH), 7.04 (d, J = 8.0 Hz, 2H, ArH), 3.58 (s,
3H, OCH3), 3.49–3.42 (m, 1H, CH), 2.54 (dd, J1 = 15.6 Hz, J2 =
6.0 Hz, 1H, CH2), 2.33 (dd, J1 = 15.8 Hz, J2 = 8.8 Hz, 1H, CH2),
2.25 (s, 3H, CH3), 1.22 (d, J = 6.8 Hz, 3H, CH3) ppm; 13C NMR
(100 MHz, CDCl3): δ 171.8, 137.7, 133.6, 129.6, 51.6, 41.5, 39.7,
21.0, 20.7 ppm.
The configurations of other products were assigned by
analogy.
Acknowledgements
We are grateful for financial support from the National Natural
Science Foundation of China (grant no. 21272024).
1
[α]2D5 +137.2 (c 4.19, CH2Cl2); H NMR (400 MHz, CDCl3):δ 8.10
Notes and references
(d, J = 8.8 Hz, 2H, ArH), 7.41–7.10 (m, 12H, ArH), 4.28–4.23 (m,
1H, CH), 4.00 (ABq, J = 14.0 Hz, 2H, CH2), 3.58 (d, J = 13.6 Hz,
1H, CH2), 3.45 (d, J = 13.6 Hz, 1H, CH2), 3.13–2.99 (m, 2H,
1 P. Metzner and A. Thuillier, in Sulfur Reagents in Organic
Synthesis, Academic Press, New York, 1994.
This journal is © The Royal Society of Chemistry 2014
Org. Biomol. Chem., 2014, 12, 1585–1594 | 1593

View Article Online
Paper
Organic & Biomolecular Chemistry
2 (a) M. Hara, I. Takahashi, M. Yoshida, K. Asano,
I. Kawamoto, M. Morimoto and H. Nakano, J. Antibiot.,
1989, 42, 333; (b) I. T. Harrison, B. Lewis, P. Nelson,
W. Rooks, A. Roszkowoski, A. Tomolonis and J. H. Fried,
J. Med. Chem., 1970, 13, 203.
3 J. R. Fraústo da Silva and R. J. P. Williams, in The Biological
Chemistry of the Elements, Oxford University Press,
New York, 2001.
2005, 603; (e) Y. Liu, B. F. Sun, B. M. Wang, M. Wakem and
L. Deng, J. Am. Chem. Soc., 2009, 131, 418; (f) For examples
of organocatalysed asymmetric sulfa-Michael additions
to α,β-unsaturated ketone derivatives, see: P. McDaid,
Y. G. Chen and L. Deng, Angew. Chem., Int. Ed., 2002, 41,
338; (g) L. Dai, S. X. Wang and F. E. Chen, Adv. Synth.
Catal., 2010, 352, 2137; (h) P. Ricci, A. Carlone, G. Bartoli,
M. Bosco, L. Sambri and P. Melchiorre, Adv. Synth. Catal.,
2008, 350, 49; (i) J. Skarżewski, M. Zielińska-Błajet and
I. Turowska-Tyrk, Tetrahedron: Asymmetry, 2001, 12, 1923;
( j) P. Suresh and K. Pitchumani, Tetrahedron: Asymmetry,
2008, 19, 2037; (k) H. Li, L. S. Zu, J. Wang and W. Wang,
Tetrahedron Lett., 2006, 47, 3145; (l) For examples of
organocatalysed tandem reactions of thiols, see: L. S. Zu,
J. Wang, H. Li, H. X. Xie, W. Jiang and W. Wang, J. Am.
Chem. Soc., 2007, 129, 1036.
7 For selected examples: (a) Y. Zhu, J. P. Malerich and
V. H. Rawal, Angew. Chem., Int. Ed., 2010, 49, 153;
(b) J. P. Malerich, K. Hagihara and V. H. Rawal, J. Am.
Chem. Soc., 2008, 130, 14416; (c) W. Yang and D.-M. Du,
Org. Lett., 2010, 12, 5450; (d) W. Yang and D.-M. Du, Adv.
Synth. Catal., 2011, 353, 1241; (e) W. Yang and D.-M. Du,
Chem. Commun., 2011, 47, 12706; (f) C. Min, X. Han;,
Z. Q. Liao, X. F. Wu, H.-B. Zhou and C. Dong, Adv. Synth.
Catal., 2011, 353, 2715; (g) W. Yang, Y. Yang and D.-M. Du,
Org. Lett., 2013, 15, 1190.
4 (a) M. Chaffman and R. N. Brogden, Drugs, 1985, 29, 387;
(b) R. D. Groneberg, C. J. Burns, M. M. Morrissette,
J. W. Ullrich, R. L. Morris, S. Darnbrough, S. W. Djuric,
S. M. Condon, G. M. McGeehan, R. Labaudiniere,
K. Neuenschwander, A. C. Scotese and J. A. Kline, J. Med.
Chem., 1999, 42, 541; (c) C. Apfel, D. W. Banner,
D. Bur, M. Dietz, T. Hirata, C. Hubschwerlen, H. Locher,
M. G. P. Page, W. Pirson, G. Rossé and J. L. Specklin,
J. Med. Chem., 2000, 43, 2324.
5 For examples of metal complex-catalysed asymmetric sulfa-
Michael additions to α,β-unsaturated acid derivatives, see:
(a) S. Kanemasa, Y. Oderaotoshi and E. Wada, J. Am. Chem.
Soc., 1999, 121, 8675; (b) A. M. M. Abe, S. J. K. Sauerland
and A. M. P. Koskinen, J. Org. Chem., 2007, 72, 5411;
(c) S. Kobayashi, C. Ogawa, M. Kawamura and M. Sugiura,
Synlett, 2001, 983; (d) M. Kawatsura, Y. Komatsu,
M. Yamamoto, S. Hayase and T. Itoh, Tetrahedron, 2008, 64,
3488; (e) M. Kawatsura, Y. Komatsu, M. Yamamoto,
S. Hayase and T. Itoh, Tetrahedron Lett., 2007, 48, 6480;
(f) S. J. K. Sauerland, E. Kiljunen and A. M. P. Koskinen,
Tetrahedron Lett., 2006, 47, 1291; (g) K. Matsumoto,
A. Watanabe, T. Uchida, K. Ogi and T. Katsuki, Tetrahedron
Lett., 2004, 45, 2385.
8 For synthesis of racemic compounds, see: S. Singh and
L. D. S. Yadav, Org. Biomol. Chem., 2012, 10, 3932, and
references cited therein.
9 J. W. Lee, T. H. Ryu, J. S. Oh, H. Y. Bae, H. B. Jang and
C. E. Song, Chem. Commun., 2009, 7224.
6 For examples of organocatalysed asymmetric sulfa-Michael 10 B. Vakulya, S. Varga, A. Csámpai and T. Soós, Org. Lett.,
additions to α,β-unsaturated acid derivatives, see: 2005, 7, 1967.
(a) L. Dai, H. J. Yang and F. E. Chen, Eur. J. Org. Chem., 11 J. B. Herwig, F. Stephan, T. Joachim and S. Theo, J. Org.
2011, 5071; (b) N. K. Rana and V. K. Singh, Org. Lett., 2011, Chem., 2010, 75, 3859.
13, 6520; (c) X. Q. Dong, X. Fang, H. Y. Tao, X. Zhou and 12 K. Juergen and S. H. Helmut, Ger. Offen, 1984, 3246149 A1.
C. J. Wang, Adv. Synth. Catal., 2012, 354, 1141; (d) B.-J. Li, 13 G. Puzicha, A. Levai and L. Szilagyi, Monatsh. Chem., 1988,
L. Jiang, M. Liu, Y.-C. Chen, L.-S. Ding and Y. Wu, Synlett,
119–119, 933.
1594 | Org. Biomol. Chem., 2014, 12, 1585–1594
This journal is © The Royal Society of Chemistry 2014