Enantioselective sulfur-michael addition of thioacetic acid to nitroalkenes catalyzed by bifunctional amine-thiourea catalysts

Article abstract of DOI:10.1002/hlca.201400125

An enantioselective Michael addition of thioacetic acid (AcSH) to nitroalkenes, catalyzed by a leucine-derived bifunctional amine-thiourea, was developed with high yields and moderate enantioselectivities. The thiourea-ammonium salt formed in the reaction

Full text of DOI:10.1002/hlca.201400125

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Helvetica Chimica Acta – Vol. 97 (2014)
Enantioselective Sulfur-Michael Addition of Thioacetic Acid to Nitroalkenes
Catalyzed by Bifunctional Amine-Thiourea Catalysts
by Renchao Wang and Jiaxi Xu*
State Key Laboratory of Chemical Resource Engineering, Department of Organic Chemistry, Faculty of
Science, Beijing University of Chemical Technology, Beijing 100029, P. R. China
(phone/fax: þ 86-10-64435565; e-mail: jxxu@mail.buct.edu.cn)
An enantioselective Michael addition of thioacetic acid (AcSH) to nitroalkenes, catalyzed by a
leucine-derived bifunctional amineꢀthiourea, was developed with high yields and moderate enantiose-
lectivities. The thiourea-ammonium salt formed in the reaction is identified as the active catalyst, and the
multiple H-bonding system is responsible for the stereocontrol. The resulting thioester products are
useful intermediates for the synthesis of enantiomerically enriched S-containing compounds.
Introduction. – The importance of chiral organosulfur compounds has been widely
recognized in natural products, biochemistry, and pharmaceutical chemistry. Thus,
various synthetic methods for chiral S-containing compounds have been developed
during recent years [1]. The asymmetric Michael addition of sulfur nucleophiles to
activated alkenes, known as asymmetric sulfur-Michael addition (SMA), creates a
center of chirality at the S-bound C-atom and provides an effective solution to the
synthesis of S-centered optically active compounds [2]. Alkyl or aryl thiols [3],
thiocarboxylic acids [4][5], and Na2SO3 [6] are appropriate S-nucleophiles for the
asymmetric SMAs. Lately, AcSH has attracted much interest, since it was introduced in
the asymmetric SMA to b-nitrostyrene with low-to-moderate enantioselectivity by
Wang and co-worker [4a]. Subsequently, chiral N-sulfinylurea and squaramide catalysts
have been successfully used in the enantio- and diastereoselective SMAs of thioacetic
acid to nitroalkenes [4b – 4e]. The asymmetric SMA involving AcSH and a,b-
unsaturated ketones was catalyzed either with cinchona alkaloids in the past, or
recently with amine-thiourea/urea catalysts; only low-to-moderate enantioselectivities
were achieved [5]. Considering the convenient introduction of a chiral S-bound C-atom
to the compounds and subsequent transformation to other S-containing molecules, e.g.,
thiols or sulfonic acids, the examples employing AcSH as the nucleophile in the
asymmetric SMA are lacking, and extension of the catalytic systems are highly
desirable.
Bifunctional amineꢀthiourea catalysis has emerged as a powerful tool for
promotion of several asymmetric reactions and attracted special interest in recent
years [7]. Various chiral scaffolds have been involved in the synthesis of the catalysts,
for example, (R,R)-cyclohexane-1,2-diamine and cinchona alkaloids. Amino acids, as
commercially available and inexpensive sources of chirality, can be converted to
amineꢀthiourea catalysts, and this class of catalysts has been applied to asymmetric
Michael additions, Mannich reactions, and FriedelꢀCrafts reactions, etc. [8]. To the best
ꢀ 2014 Verlag Helvetica Chimica Acta AG, Zꢁrich

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of our knowledge, asymmetric SMA, induced by amino acid derived amineꢀthiourea
catalysts, has not been attempted yet. Herein, we report our study on the asymmetric
SMA of AcSH to nitroalkenes, catalyzed with leucine-derived bifunctional catalyst,
with high yield and up to 70% ee.
Results and Discussion. – First, amineꢀthiourea catalysts 3 (1-(2-aminocyclohexyl)-
3-[3,5-bis(trifluoromethyl)phenyl]thioureas) based on (R,R)-cyclohexane-1,2-diamine
and 4 (1-[3,5-bis(trifluoromethyl)phenyl]-3-[piperidin-1-ylalkyl]thioureas), derived
from l-amino acids, were synthesized and tested in the enantioselective sulfur-Michael
addition of AcSH to (E)-b-nitrostyrene ((E)-1-nitro-2-phenylethene; 1a). As shown in
Table 1, the structure of the amineꢀthiourea catalysts played an important role in the
stereocontrol of the reaction. Catalyst 3a bearing a primary amine group afforded the
product 2a with high yield but low enantioselectivity, while the enantioselectivity was
increased with the tertiary amineꢀthiourea 3b. Catalyst 3c with a bulkier amino group
provided results similar to those with catalyst 3b (Table 1, Entries 1 – 3). The reactions
were complete within 0.5 h when catalyzed with 10 mol-% of 4, and enantioselectivities
in the range of 38 – 53% were observed. Among the four catalysts derived from
different l-amino acids, leucine-derived 4c proved to be preferable (Table 1, Entries
Table 1. Asymmetric Michael Addition of AcSH to (E)-b-Nitrostyrene Catalyzed by Organocatalystsa)
Entry
Catalyst
Yield [%]b)
ee [%]c)
1
2
3
4
5
6
7
8
3a
3b
3c
4a
4b
4c
4d
5
91
99
96
98
91
94
93
96
ꢀ 30
ꢀ 51
ꢀ 50
41
38
53
40
55
a) The reaction was carried out with (E)-b-nitrostyrene (29.8 mg, 0.20 mmol) and AcSH (30.5 mg,
0.028 ml, 0.40 mmol) in the presence of 10 mol-% organocatalyst in 2 ml of Et2O at 08 for 0.5 h. b) Yield
of isolated 2a. c) Determined by HPLC analysis with an AS-H chiral column; ꢀ means (R)-form in
excess.

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Helvetica Chimica Acta – Vol. 97 (2014)
4 – 7). The replacement of the piperidin-1-yl group in 4c with the Me2N group provided
catalyst 5, which promoted the reaction with 96% yield and 55% ee, i.e., the best result
attained (Table 1, Entry 8).
The reaction conditions were further optimized by using catalyst 5, and the results
are compiled in Table 2. First, different solvents were examined, and Et2O turned out to
be the best medium for the reaction regarding the enantioselectivity (Table 2, Entries
i
1 – 10). The reaction in PrOH resulted in a dramatic loss of the stereoselectivity,
probably due to the strong H-bond donor ability of the alcohol. The reactions displayed
little differences when carried out with 10 mol-% of AcOH or PhCOOH as additive,
and this phenomenon indicated that the interaction between the thioacetate and the
catalyst/(E)-b-nitrostyrene (1a) was weak, accordingly the key to stereocontrol was the
coordination state between the catalyst and 1a (Table 2, Entries 11 and 12). Changing
the substrate-addition order, i.e., adding 1a to a solution of catalyst 5 and AcSH also
provided the product 2a with 55% ee (Table 2, Entry 13). Considering that the
acidꢀbase neutralization reaction is much faster than the Michael addition, these
Table 2. Optimization of Reaction Conditions for Asymmetric Michael Addition of AcSH to (E)-b-
Nitrostyrenea)
Entry
Solvent
T [8]
Yield [%]b)
ee [%]c)
1
2
3
4
5
6
7
8
9
10
11d)
12e)
13f)
14
15
16
17g)
18h)
19i)
Et2O
0
0
0
0
0
0
0
0
0
0
0
0
0
96
95
97
94
98
90
96
96
91
94
98
93
97
94
96
96
93
94
90
55
53
54
47
52
44
48
40
48
23
55
56
55
59
61
61
55
59
57
iPr2O
tBuOMe
THF
CH2Cl2
CHCl3
Toluene
Acetone
AcOEt
iPrOH
Et2O
Et2O
Et2O
Et2O
Et2O
ꢀ 10
ꢀ 20
ꢀ 30
ꢀ 20
ꢀ 20
ꢀ 20
Et2O
Et2O
Et2O
Et2O
a) The reaction was carried out with (E)-b-nitrostyrene (14.9 mg, 0.10 mmol) and AcSH (15.2 mg,
0.014 ml, 0.20 mmol) in the presence of 10 mol-% organocatalyst 5 in 1 ml of solvent. b) Yield of isolated
2a. c) Determined by HPLC analysis with an AS-H chiral column. d) Ten mol-% PhCOOH was added.
f
e) Ten mol-% AcOH was added. ) (E)-b-Nitrostyrene (1a) was added to a solution of 5 and AcSH.
i
g) Five mol-% catalyst. h) Two mol-% catalyst. ) One mol-% catalyst.

Helvetica Chimica Acta – Vol. 97 (2014)
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results indicated that the AcSH reacted with the tertiary amino group of catalyst 5 first,
generating thioacetate and 5 · Hþ. Then, (E)-b-nitrostyrene (1a) was activated by 5 · Hþ
and attacked by thioacetate, thus generating product 2a with 55% ee. Racemization of
the enantiomerically enriched product occurred slowly, when the product was treated
with catalyst 5 in Et2O under neutral conditions, whereas no racemization was observed
under acidic conditions. Considering the reversibility of the SMA, catalyst 5 itself failed
to arrange the reaction enantioselectively, while 5 · Hþ, with an additional H-bond
donor provided by the ammonium salt, seemed to be the real catalyst for the reaction.
The multiple H-bonding system including two thiourea H-bondings and an ammonium
salt H-bonding in 5 · Hþ seemed to be essential to attain good stereocontrol. The benefit
of the multiple H-bonding system in asymmetric reactions was also reported in the
literature (Scheme) [3r][9]. These studies indicated that the reaction must be run
under acidic conditions, and use of excess AcSH was necessary.
Lowering the reaction temperature to ꢀ 208 improved the product ee, which
remained unchanged when the reaction was carried out at ꢀ 308 (Table 2, Entries 14 –
16). The selectivity slightly decreased with lower catalyst loading, and 2 mol-% catalyst
loading furnished 2a with 94% yield and 59% ee (Table 2, Entries 17 – 19). The absolute
configuration of product 2a was determined as (S) by comparison of its specific rotation
with that reported in [4d].
The scope of the substrates was investigated after establishing the best reaction
conditions. The present system tolerated electron-withdrawing or electron-donating
groups on the aromatic ring of the substrates, and, generally, ortho-substitution on the
aromatic ring had a beneficial impact on the enantioselectivity (Table 3, Entries 1 – 10).
The phenomenon was also observed in other asymmetric Michael additions. For
substrate 1f, the NO2 group on the aromatic ring probably interfered with the H-bond
interaction between the catalyst and the substrate, thus lowering the enantioselectivity.
Substrate 1k bearing a naphthalen-1-yl group reacted with AcSH to give product 2k
with 93% yield and 70% ee. Besides the aromatic nitroalkenes, aliphatic nitroalkenes
Scheme. Multiple H-bonding System Used in This Work and Examples Reported in Literature

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Helvetica Chimica Acta – Vol. 97 (2014)
Table 3. Michael Addition Reactions of AcSH to (E)-Nitroalkenesa)
Entry
2
R
Yield [%]b)
ee [%]c)
1
2
3
4
5
6
7
8
9
2a
2b
2c
2d
2e
2f
2g
2h
2i
Ph
94
96
90
92
99
89
96
98
96
91
93
85
59
62
57
49
58
38
64
62
59
68
70
57
2-ClꢀC6H4
4-ClꢀC6H4
2,6-Cl2ꢀC6H3
4-BrꢀC6H4
2-O2NꢀC6H4
4-MeꢀC6H4
4-MeOꢀC6H4
3-MeOꢀC6H4
2,4-(MeO)2ꢀC6H3
Naphthalen-1-yl
iPr
10
11
12
2j
2k
2l
a) The reaction was carried out with (E)-nitroalkene (0.10 mmol) and AcSH (15.2 mg, 0.014 ml,
0.20 mmol) in the presence of 2 mol-% organocatalyst 5 in Et2O at ꢀ 208. b) Yield of isolated product.
c) Determined by HPLC analysis with an AS-H or AD-H chiral column.
were also suitable substrates for this catalysis system with high yields and moderate ee
values (Table 3, Entry 12).
3. Conclusions. – We have developed the l-leucine-derived bifunctional thiourea-
catalyzed asymmetric sulfur-Michael addition of AcSH to nitroalkenes with a broad
substrate scope, high yields, and up to 70% ee. Detailed analysis of the catalytic system
revealed that the catalyst reacts with AcSH prior to nitroalkenes, and a multiple H-
bond system seems to be necessary to achieve a good stereocontrol. This method
expands the application scope of the amino acid-derived amineꢀthiourea catalysts and
offers a convenient way to chiral organosulfur compounds.
Experimental Part
General. Column chromatography (CC): silica gel (SiO2, 200 – 300 mesh). M.p.: Yanaco MP-500;
uncorrected. The ee values [%] were determined by chiral HPLC using an Agilent 1260 LC instrument
with a Daicel Chiralpak AS-H or AD-H column. Optical rotations: Anton Paar MCP 200 polarimeter.
1H- and 13C-NMR spectra: Bruker at 300 and 400 MHz, resp.; in CDCl3; d in ppm rel. to Me4Si as internal
standard; J in Hz. HR-MS: Agilent LC/MDF TOF mass spectrometer; in m/z.
General Procedure for Asymmetric Sulfur-Michael Addition of AcSH to Nitroalkenes. A soln. of
nitroalkene (0.1 mmol) and catalyst 5 (0.83 mg, 0.002 mmol) was stirred at ꢀ 208 in Et2O (1 ml). AcSH
(15.2 mg, 0.014 ml, 0.2 mmol) was added, and the reaction was monitored by TLC. After completion of
the reaction, the soln. was washed quickly with sat. aq. NaHCO3 soln. (3 ꢁ 1 ml), and eluted immediately
through a silica-gel plug with Et2O. After evaporation of the solvent in vacuo, the residue was purified by
CC to give the desired product 2.
S-[(1S)-2-Nitro-1-phenylethyl] Ethanethioate (2a). Chiral HPLC (AS-H; hexane/iPrOH 70 :30;
1.0 ml/min; l 220 nm): tR(major) 10.2, tR(minor) 13.4 min. Colorless crystals. Yield: 94%. M.p. 126 – 1298

Helvetica Chimica Acta – Vol. 97 (2014)
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([4d]: 122 – 1248). [a]2D2 ¼ þ143.4 (c ¼ 0.8, CHCl3) ([4d]: [a]2D2 ¼ þ136.4 (c ¼ 0.9, CH2Cl2)). 1H-NMR
(300 MHz, CDCl3): 2.36 (s, Me); 4.84 (d, J ¼ 7.5, CH2); 5.29 (t, J ¼ 7.5, CH); 7.32 – 7.35 (m, 5 arom. H).
13C-NMR (75 MHz, CDCl3): 30.3; 44.4; 77.9; 127.7; 128.8; 129.1; 135.6; 193.3.
S-[(1S)-1-(2-Chlorophenyl)-2-nitroethyl] Ethanethioate (2b). Chiral HPLC (AS-H; hexane/iPrOH
70 :30; 1.0 ml/min; l 220 nm): tR(major) 9.6, tR(minor) 13.3 min. Colorless oil. Yield: 96%. [a]2D2 ¼ þ15.1
(c ¼ 0.9, CHCl3). 1H-NMR (400 MHz, CDCl3): 2.37 (s, Me); 4.87 (dd, J ¼ 6.4, 13.6, 1 H of CH2); 5.00 (dd,
J ¼ 8.8, 13.6, 1 H of CH2); 5.71 (dd, J ¼ 6.4, 8.8, CH); 7.25 – 7.27 (m, 2 arom. H); 7.36 – 7.42 (m, 2 arom. H).
13C-NMR (100 MHz, CDCl3): 30.2; 41.9; 76.6; 127.4; 129.5; 130.0; 130.5; 133.2; 138.7; 193.0. HR-ESI-MS:
281.9965 ([M þ Na]þ, C10H10ClNNaO3Sþ; calc. 281.9968).
S-[(1S)-1-(4-Chlorophenyl)-2-nitroethyl] Ethanethioate (2c). Chiral HPLC (AS-H; hexane/iPrOH
70 :30; 1.0 ml/min; l 220 nm): tR(major) 12.9, tR(minor) 16.8 min. Colorless crystals. Yield: 90%. M.p.
60 – 638 ([4e]: 67 – 688). [a]2D2 ¼ þ144.8 (c ¼ 0.9, CHCl3). 1H-NMR (400 MHz, CDCl3): 2.36 (s, Me); 4.79
(dd, J ¼ 9.0, 13.4, 1 H of CH2); 4.84 (dd, J ¼ 6.6, 13.4, 1 H of CH2); 5.25 (dd, J ¼ 6.6, 9.0, CH); 7.26 (d, J ¼
8.6, 2 arom. H); 7.33 (d, J ¼ 8.6 Hz, 2 arom. H). 13C-NMR (100 MHz, CDCl3): 30.3; 43.7; 77.7; 129.1;
129.3; 134.2; 134.7; 193.0.
S-[(1S)-1-(2,6-Dichlorophenyl)-2-nitroethyl] Ethanethioate (2d). Chiral HPLC (AS-H; hexane/
iPrOH 70 :30; 1.0 ml/min; l 220 nm): tR(major) 8.6, tR(minor) 9.0 min. Colorless crystals. Yield: 92%.
M.p. 66 – 678. [a]2D2 ¼ þ76.2 (c ¼ 1.0, CHCl3). 1H-NMR (400 MHz, CDCl3): 2.38 (s, Me); 4.87 (dd, J ¼ 6.8,
13.2, 1 H of CH2); 5.22 (dd, J ¼ 8.8, 13.2, 1 H of CH2); 6.43 (dd, J ¼ 6.8, 8.8, CH); 7.20 (t, J ¼ 8.0, 1 arom.
H); 7.31 (d, J ¼ 8.0, 1 arom. H); 7.37 (d, J ¼ 8.0, 1 arom. H). 13C-NMR (100 MHz, CDCl3): 30.0; 39.8; 76.2;
129.2; 129.6; 130.2; 132.0; 135.4; 136.2; 192.6. HR-ESI-MS: 315.9579 ([M þ Na]þ, C10H9Cl2NNaO3Sþ;
calc. 315.9578).
S-[(1S)-1-(4-Bromophenyl)-2-nitroethyl) Ethanethioate (2e). Chiral HPLC (AS-H; hexane/iPrOH
70 :30; 1.0 ml/min; l 220 nm): tR(major) 11.5, tR(minor) 13.7 min. Colorless crystals. Yield: 99%. M.p.
1
74 – 768. [a]2D2 ¼ þ164.0 (c ¼ 0.4, CHCl3). H-NMR (400 MHz, CDCl3): 2.36 (s, Me); 4.80 (dd, J ¼ 9.2,
13.2, 1 H of CH2); 4.82 (dd, J ¼ 6.8, 13.2, 1 H of CH2); 5.24 (dd, J ¼ 6.8, 9.2, CH); 7.18 – 7.21 (m, 2 arom.
H); 7.46 – 7.49 (m, 2 arom. H). 13C-NMR (100 MHz, CDCl3): 30.3; 43.8; 77.6; 122.9; 132.3; 134.8; 192.9.
HR-ESI-MS: 325.9459 ([M þ Na]þ. C10H10BrNNaO3Sþ; 325.9462).
S-[(1S)-1-(2-Nitro-1-(2-nitrophenyl)ethyl) Ethanethioate (2f). Chiral HPLC (AS-H; hexane/iPrOH
70 :30; 1.0 ml/min; l 220 nm): tR(major) 19.2, tR(minor) 24.9 min. Colorless oil. Yield: 89%. [a]2D2 ¼ þ3.4
(c ¼ 0.8, CHCl3). 1H-NMR (400 MHz, CDCl3): 2.35 (s, Me); 4.96 (dd, J ¼ 6.4, 13.6, 1 H of CH2); 5.03 (dd,
J ¼ 7.6, 13.6, 1 H of CH2); 5.87 (dd, J ¼ 6.4, 7.6, CH); 7.49 – 7.53 (m, 1 arom. H); 7.57 – 7.66 (m, 2 arom. H);
7.98 – 8.00 (m, 1 arom. H). 13C-NMR (100 MHz, CDCl3): 30.1; 40.7; 77.5; 125.5; 129.7; 130.9; 131.4; 133.7;
148.5; 192.6. HR-ESI-MS: 293.0203 ([M þ Na]þ, C10H10N2NaO5Sþ; calc. 293.0208).
S-[(1S)-1-(4-Methylphenyl)-2-nitroethyl] Ethanethioate (2g). Chiral HPLC (AS-H; hexane/iPrOH
70 :30; 1.0 ml/min; l 220 nm): tR(major) 8.6, tR(minor) 11.3 min. Colorless crystals. M.p. 80 – 818 ([4b]:
91 – 928). Yield: 96%. [a]2D2 ¼ þ153.5 (c ¼ 0.9, CHCl3) ([4b]: [a]2D3 ¼ ꢀ159.1 (c ¼ 1.0, CHCl3; (R)-
enantiomer). 1H-NMR (400 MHz, CDCl3): 2.32 (s, Me); 2.34 (s, Me); 4.82 (dd, J ¼ 8.4, 13.2, 1 H of CH2);
4.82 (dd, J ¼ 7.2, 13.2, 1 H of CH2); 5.25 (dd, J ¼ 7.2, 8.4, CH); 7.14 (d, J ¼ 8.4, 2 arom. H); 7.19 (d, J ¼ 8.4, 2
arom. H). 13C-NMR (100 MHz, CDCl3): 21.1; 30.3; 44.2; 78.0; 127.6; 129.8; 132.5; 138.7; 193.4.
S-[(1S)-1-(4-Methoxyphenyl)-2-nitroethyl] Ethanethioate (2h). Chiral HPLC (AS-H; hexane/iPrOH
70 :30; 1.0 ml/min; l 220 nm): tR(major) 20.1, tR(minor) 30.8 min. Colorless crystals. M.p. 111 – 1148 ([4b]:
105 – 1068). Yield: 98%. [a]2D2 ¼ þ139.9 (c ¼ 1.1, CHCl3) ([4b]: [a]D23 ¼ ꢀ234.3 (c ¼ 1.0, CHCl3; (R)-
1
enantiomer). H-NMR (400 MHz, CDCl3): 2.34 (s, Me); 3.78 (s, MeO); 4.80 (dd, J ¼ 9.2, 13.2, 1 H of
CH2); 4.81 (dd, J ¼ 6.8, 13.2, 1 H of CH2); 5.24 (dd, J ¼ 6.4, 9.2, CH); 6.86 (d, J ¼ 8.8, 2 arom. H); 7.23 (d,
J ¼ 8.8, 2 arom. H). 13C-NMR (100 MHz, CDCl3): 30.3; 44.1; 55.3; 78.1; 114.5; 127.4; 128.9; 159.8; 193.5.
S-[(1S)-1-(3-Methoxyphenyl)-2-nitroethyl] Ethanethioate (2i). Chiral HPLC (AS-H; hexane/iPrOH
70 :30; 1.0 ml/min; l 220 nm): tR(major) 11.4, tR(minor) 12.6 min. Colorless oil. Yield: 96%. [a]2D2 ¼ þ42.1
(c ¼ 1.0, CHCl3). 1H-NMR (400 MHz, CDCl3): 2.35 (s, Me); 3.79 (s, MeO); 4.82 (d, J ¼ 8.0, CH2); 5.26 (t,
J ¼ 8.0, CH); 6.83 – 6.89 (m, 3 arom. H); 7.23 – 7.28 (m, 1 arom. H). 13C-NMR (100 MHz, CDCl3): 30.3;
44.4; 55.3; 77.9; 113.6; 114.1; 119.8; 130.2; 137.1; 160.0; 193.3. HR-ESI-MS: 278.0461 ([M þ Na]þ,
C11H13NNaO4Sþ; calc. 278.0463).

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Helvetica Chimica Acta – Vol. 97 (2014)
S-[(1S)-1-(2,4-Dimethoxyphenyl)-2-nitroethyl] Ethanethioate (2j) [4a]. Chiral HPLC (AS-H;
hexane/iPrOH 70 :30; 1.0 ml/min; l 220 nm): tR(major) 9.9, tR(minor) 11.5 min. Colorless oil. Yield:
91%. [a]2D2 ¼ þ131.1 (c ¼ 0.9, CHCl3). 1H-NMR (400 MHz, CDCl3): 2.32 (s, Me); 3.78 (s, MeO); 3.85 (s,
MeO); 4.77 (dd, J ¼ 6.4, 13.2, 1 H of CH2); 4.95 (dd, J ¼ 8.8, 12.8, 1 H of CH2); 5.43 (dd, J ¼ 6.4, 9.2, CH);
6.41 – 6.45 (m, 2 arom. H); 7.19 (d, J ¼ 8.0, 1 arom. H). 13C-NMR (100 MHz, CDCl3): 30.2; 41.2; 55.3;
55.6; 77.2; 99.2; 104.5; 116.0; 130.6; 158.3; 161.3; 194.2.
S-[(1S)-1-(Naphthalen-1-yl)-2-nitroethyl] Ethanethioate (2k). Chiral HPLC (AS-H; hexane/iPrOH
70 :30; 1.0 ml/min; l 220 nm): tR(major) 10.8, tR(minor) 16.0 min. Colorless crystals. Yield: 93%. M.p.
69 – 698. [a]2D2 ¼ þ133.8 (c ¼ 1.1, CHCl3). 1H-NMR (400 MHz, CDCl3): 2.35 (s, Me); 4.96 (dd, J ¼ 7.2, 9.6,
1 H of CH2); 5.10 (dd, J ¼ 8.8, 9.6, 1 H of CH2); 6.16 (dd, J ¼ 7.2, 8.8, CH); 7.41 (t, J ¼ 7.6, 1 arom. H); 7.46
(d, J ¼ 7.6, 1 arom. H); 7.52 (t, J ¼ 7.2, 1 arom. H); 7.58 – 7.62 (m, 1 arom. H); 7.81 (d, J ¼ 8.0, 1 arom. H);
7.86 (d, J ¼ 8.0, 1 arom. H); 8.10 (d, J ¼ 8.4, 1 arom. H). 13C-NMR (100 MHz, CDCl3): 30.1; 40.2; 77.4;
122.5; 125.1; 126.3; 127.1; 129.2; 129.5; 130.4; 131.1; 134.1; 193.6. HR-ESI-MS: 298.0514 ([M þ Na]þ,
C14H13NNaO3Sþ; calc. 298.0514).
S-[(2S)-3-Methyl-1-nitrobutan-2-yl] Ethanethioate (2l) [4e]. Chiral HPLC (AD-H; hexane/iPrOH
70 :30; 1.0 ml/min; l 220 nm): tR(major) 5.3, tR(minor) 5.6 min. Colorless oil. Yield: 85%. [a]2D2 ¼ ꢀ1.6
(c ¼ 0.4, CHCl3). 1H-NMR (400 MHz, CDCl3): 0.97 (d, J ¼ 6.8, Me); 1.02 (d, J ¼ 6.8, Me); 2.03 – 2.11 (m,
CH); 2.37 (s, Me); 4.14 – 4.19 (m, CH); 4.54 (dd, J ¼ 6.8, 13.2, 1 H of CH2); 4.57 (dd, J ¼ 7.6, 13.2, 1 H of
CH2). 13C-NMR (100 MHz, CDCl3): 18.5; 20.2; 29.4; 30.7; 47.5; 77.0; 193.7.
The work was supported by the National Basic Research Program of China (No 2013CB328905) and
National Natural Science Foundation of China (Nos. 21372025, 21172017, and 20092013).
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Received April 8, 2014