Direct asymmetric Michael addition of thioether-based aryl sulfanyl-propan-2-one to nitroalkenes catalyzed by a chiral amine-thiourea bifunctional organocatalyst

Article abstract of DOI:10.1002/chir.20689

Although the organocatalytic direct asymmetric Michael reactions of carbonyl compounds to nitroalkenes have been investigated intensely, the Michael reaction of the thioether-based donors remains a rather undeveloped field. This work concerns the asymmetric Michael addition of aryl sulfanyl-propan-2-one to nitroalkenes with benzoic acid as an additive, and chiral amine-thiourea as a bifunctional organocatalyst. The reactions provided the highly functionalized chiral adducts with excellent enantioselectivities (up to 96% ee) and good yields. Moreover, the further transformed products exhibited excellent diastereoselectivity.

Full text of DOI:10.1002/chir.20689

CHIRALITY 22:625–634 (2010)
Direct Asymmetric Michael Addition of Thioether-based Aryl
Sulfanyl-propan-2-one to Nitroalkenes Catalyzed by a Chiral
Amine-Thiourea Bifunctional Organocatalyst
XIANXING JIANG,1,2 BANGZHI ZHANG,2 YIFU ZHANG,2 LI LIN,2 WENJIN YAN,2 AND RUI WANG1,2
*
1State Key Laboratory for Oxo Synthesis and Selective Oxidation, Lanzhou Institute of Chemical Physics,
Chinese Academy of Sciences, Lanzhou 730000, China
2State Key Laboratory of Applied Organic Chemistry, Institute of Biochemistry and Molecular Biology,
Lanzhou University, Lanzhou 730000, China
ABSTRACT
Although the organocatalytic direct asymmetric Michael reactions of
carbonyl compounds to nitroalkenes have been investigated intensely, the Michael reac-
tion of the thioether-based donors remains a rather undeveloped field. This work con-
cerns the asymmetric Michael addition of aryl sulfanyl-propan-2-one to nitroalkenes
with benzoic acid as an additive, and chiral amine-thiourea as a bifunctional organocata-
lyst. The reactions provided the highly functionalized chiral adducts with excellent
enantioselectivities (up to 96% ee) and good yields. Moreover, the further transformed
C
VV
products exhibited excellent diastereoselectivity. Chirality 22:625–634, 2010.
2010
Wiley-Liss, Inc.
KEY WORDS: asymmetric Michael addition; aryl sulfanyl-propan-2-one; nitroalkenes;
thiourea; bifunctional organocatalyst
INTRODUCTION
asymmetric Michael reaction of thioether-based donors
remains a much less developed field and other efficient
organocatalytic systems still need to be investigated.
The organocatalytic direct asymmetric Michael reaction
as one of the most powerful and efficient methods for the
formation of carbon-carbon bonds in organic synthesis has
attracted great attention in the past decades.1–9 Many
enantioselective Michael reactions of malonates, alde-
hydes, and ketones to nitroalkenes by using chiral organo-
catalysts have been reported to date. However, the Mi-
chael reaction of the thioether-based donors has proven to
be a formidable challenge. The versatility of thioethers or
chiral organic molecules bearing thioether substituents,
for example a phenylthio group, in organic synthesis, bio-
logical and chemical transformation process has been rec-
ognized widely. The use of this functional group in Pum-
merer reaction is the important methodology for the syn-
thesis of heterocyclic compounds,10,11 and this functional
group can be further transformed into other versatile func-
tionalities, such as carbonyl functionality (direct oxidative
desulfuration)12 and sulfonyl functionality.13 Furthermore,
the use of sulfonyl functionality as an auxiliary group is a
very useful synthetic strategy because this functional
group can act as an electron-withdrawing group or as a
EXPERIMENTAL
General Remarks
All reactions were carried out under an argon atmos-
phere condition unless otherwise noted, solvents were
dried according to established procedures. Reactions were
monitored by thin layer chromatography (TLC), column
chromatography purifications were carried out using silica
gel. (R)-1-Phenylethyl isothiocyanate, 1,2-diaminocyclohex-
ane, N,N0-dicyclohexylcarbodiimide, lithium hexamethyldi-
silazide (LiHMDS), 1-hydroxybenzotriazol (HOBt), and
lithium diisopropylamide (LDA) (2 M solution in THF)
were commercially available from Acros and Aldrich. 1H
NMR spectra were recorded on Brucker 200 MHz, 300
MHz, and 400 MHz spectrometer in CDCl3 unless other-
wise noted and 13C NMR spectra were recorded on
leaving group and can be substituted by an alkyl group, a Contract grant sponsor: Natural Science Foundation of China;
Contract grant numbers: 20525206, 20772052, 20621091.
Contract grant sponsor: Chang Jiang Program of the Ministry of Educa-
tion of China.
carbonyl functionality or a nucleophile as well as undergo
a b-elimination process.14–23 In addition, a variety of thio-
*Correspondence to: Rui Wang, State Key Laboratory for Oxo Synthesis
and Selective Oxidation, Lanzhou Institute of Chemical Physics, Chinese
Academy of Sciences, Lanzhou 730000, China.
E-mail: wangrui@lzu.edu.cn
ethers like acetyl-CoA, propionyl-CoA, and malonyl-CoA
are important synthase enzymes in biochemical transfor-
mation process.24–28 Recently, Barbas and coworkers29
Received for publication 16 August 2008; Accepted 10 November 2008
reported the first organocatalytic Michael addition of tri-
DOI: 10.1002/chir.20689
fluoroethyl thioesters to nitroalkenes by using trialkylsilyl-
Published online 8 February 2010 in Wiley InterScience
protected diarylprolinol as a catalyst. Nevertheless, the
(www.interscience.wiley.com).
C
VV
2010 Wiley-Liss, Inc.

626
JIANG ET AL.
Brucker 200 MHz, 300 MHz, and 400 MHz spectrometer EtOAc in hexanes, the product 2f as a white solid was iso-
in CDCl3 using tetramethylsilane (TMS) as internal stand- lated in 86% yield (1.9 g).
ard unless otherwise noted. Data are presented as follows:
General Procedure for the Asymmetric Addition of
Thioether-Based Aryl Sulfanyl-propan-2-one to
chemical shift, integration, multiplicity (br 5 broad, s 5
singlet, d 5 doublet, t 5 triplet, q 5 quartet, m 5 multip-
let, cm 5 complex multiplet) and coupling constant in
Nitroalkenes
Hertz (Hz). Infrared (IR) spectra were recorded on a FTIR
spectrometer. Melting points were measured on an XT-4
melting point apparatus and were uncorrected. Optical
rotations were recorded on a Perkin-Elmer 341 polarime-
ter. HR-MS was measured with an APEX II 47e mass spec-
trometer. The ee values determination was carried out
using chiral high-performance liquid chromatography
(HPLC) with Daicel Chiracel OD-H, AD-H or AS-H column
on Waters with a 2996 UV-detector and the Dr values
determined by 400 Hz 1H NMR.
To a stirred solution of 2d (8.4 mg, 0.03 mmol, 15 mol
%), aryl sulfanyl-propan-2-one (0.2 mmol) and benzoic acid
(3.7 mg, 0.03 mmol) in toluene (0.6 ml) under argon, nitro-
alkene (0.6 mmol) was added. The solution was stirred at
08C for 2 h, and then stirred at 208C. After the reaction
was completed (monitored by TLC), the resulting mixture
was concentrated under reduced pressure and the residue
was purified through column chromatography on silica gel
(eluent, EtOAc/hexane 1:9) to give the optical pure prod-
uct. The enantiomeric purity of the product was deter-
mined by using HPLC and the Dr values determined by
400 MHz 1H NMR.
The catalyst 2b was synthesized according to literature
procedure.30
Characterizations of the Products:
Typical Procedure for the Synthesis of 2c
(S)-Diphenyl(pyrrolidin-2-yl)methanol 2b. [a]2D0
5
A solution of N,N0-dicyclohexylcarbodiimide (2.1 g, 10
mmol) in dry dichloromethane (CH2Cl2) (8.0 ml) was
slowly added to a solution of N-(tert-butoxycarbonyl)-L-pro-
line (2.15 g, 10.0 mmol) and HOBt (1.35 g, 10.0 mmol) in
dry CH2Cl2 (30 ml) and dimethyl formamide (DMF) (5.0
ml) at 08C. The solution was stirred at the same tempera-
ture for 3 h. Then, the reaction mixture was stirred at
room temperature for 12 h. After filtration and optically
pure amino alcohol 2b (2.3 g, 9.0 mmol) was added at 08C
and the resulting solution was stirred for 12 h at room tem-
perature. The solvent was removed at reduced pressure
and the residue was purified through column chromatog-
raphy on silica gel (eluent, EtOAc/hexane 1:3) to give the
white solid in 65% yield (2.64 g). TFA (15 ml) was slowly
added to a solution of the above product (2.64 g, 5.86
mmol) in dry CH2Cl2 at 08C and the resulting solution was
stirred for 2 h. Excess TFA was carefully neutralized by
adding solid sodium bicarbonate and the whole mixture
was extracted with CH2Cl2. The organic layer was dried
and the solvent was removed to obtain pure product 2c
(1.9 g).
1
260 (c 5 1.0, MeOH); mp 79–818C. H NMR (400 MHz):
d 7.56(d, J 5 8.4 Hz, 2H), 7.51(d, J 5 8.4 Hz, 2H), 7.26–
7.31(m, 4H), 7.14–7.19 (m, 2H), 4.26 (t, 1H), 2.99–3.05 (m,
1H), 2.93 (dd, J 5 8.8 Hz, 16.8 Hz, 1H), 1.69–1.76 (m, 2H),
1.54–1.67 (m, 2H); 13C NMR (100 MHz): d 148.0, 145.3,
128.2, 127.9, 126.5, 126.3, 125.9, 125.5, 77.3, 64.5, 46.7,
26.3, 25.5. HRMS-ESI (m/z): calcd for C17H19NO [M
1H]1: 254.1539; found: 254.1538, 0.4 ppm.
[(S)-2-(hydroxydiphenylmethyl)pyrrolidin-1-yl][(S)-
pyrrolidin-2-yl]methanone 2c. [a]2D0 5 270 (c 5 1.0,
MeOH); mp 167–1688C. 1H NMR (400 MHz): d 7.41 (d, J
5 7.2 Hz, 2H), 7.36 (d, J 5 7.6 Hz, 2H), 7.22–7.30 (m, 6H),
5.12 (t, 1H), 3.72 (t, 1H), 3.44–3.50 (m, 1H), 3.04-3.10(m,
1H), 2.86 (dd, J 5 8.4 Hz, 17.6 Hz, 1H), 2.77 (dd, J 5 7.2
Hz, 17.2 Hz, 1H), 2.08(br, 1H), 1.96–2.06(m, 1H), 1.84–
1.94 (m, 2H), 1.65–1.72(m, 1H), 1.50–1.61(m, 2H), 1.17–
1.25(m, 2H); 13C NMR (100 MHz): d 176.4, 145.7, 143.0,
127.9, 127.8, 127.7, 127.4, 127.3, 127.2, 81.8, 68.1, 59.7,
47.9, 47.5, 30.2, 29.5, 26.1, 23.6. IR: 3298, 3155, 2975, 2880,
2253, 1794, 1615, 1449, 1408, 1174, 1098, 908, 735, 651
cm21. HRMS-ESI (m/z): calcd for C22H26N2O2 [M 1 H]1:
351.2067; found: 351.2069, 0.6 ppm.
The chiral primary amine-thiourea 2d, 2e, and 2f were
synthesized according to literature procedures.31
1-[(1R,2R)-2-Aminocyclohexyl]-3-[(R)-1-phenyleth-
yl]thiourea 2d. [a]2D0 5 136 (c 5 1.1, CHCl3); mp 59–
608C. 1H NMR (400 MHz, [D6]DMSO): d 7.22–7.31 (m,
5H), 5.43 (br, 1H), 3.66 (br, 1H), 2.40–2.50 (m, 1H), 1.94–
1.99 (m, 1H), 1.72–1.79 (m, 1H),1.47–1.58 (m, 2H), 1.39
(d, J 5 6.8 Hz, 3H), 0.84–1.17 (m, 4H); 13C NMR (100
MHz, [D6]DMSO): d 144.5, 128.3, 126.7, 126.1, 59.6, 54.2,
52.3, 34.4, 31.4, 24.6, 24.5, 22.6. HRMS-ESI (m/z): calcd for
C15H23N3S [M 1 H]1: 278.1685; found: 278.1684, 0.4 ppm.
Typical Procedures for the Synthesis of 2d, 2e, and 2f
(R)-1-Phenylethyl isothiocyanate (10 mmol, 1.63 mg)
was added over a period of 1.5 h to a stirred solution of
(R,R)-1,2-diaminocyclohexane (10 mmol, 1.14 g) in dry
CH2Cl2 (50 ml). The reaction mixture was stirred for a fur-
ther 3 h at room temperature. The solvent was removed
under reduced pressure. After column chromatography on
silica gel eluted with 60% EtOAc in hexanes, the product
2d as a white solid was isolated in 62% yield (1.7 g).
(R)-1-Phenylethyl isothiocyanate (10 mmol, 1.63 mg)
1-[(1S,2S)-2-Aminocyclohexyl]-3-[(R)-1-phenyleth-
was added to a stirred solution of (R,R)-1,2-diaminocyclo- yl]thiourea 2e. [a]2D0 5 289 (c 5 1.4, CHCl3); mp 62–
hexane (5.0 mmol, 0.57 g) in dry CH2Cl2 (30 ml). The 638C. 1H NMR (400 MHz, [D6]DMSO): d 7.11–7.30 (m,
reaction mixture was stirred for 5 h at room temperature. 5H), 5.40 (br, 1H), 3.65 (br, 1H), 2.36–2.48 (m, 1H), 1.91–
The solvent was removed under reduced pressure. After 1.96 (m, 1H), 1.74–1.77 (m, 1H),1.55–1.67 (m, 2H), 1.38
column chromatography on silica gel eluted with 25% (d, J 5 6.8 Hz, 3H), 0.99–1.29 (m, 4H); 13C NMR (100
Chirality DOI 10.1002/chir

MICHAEL ADDITION OF ARYL SULFANYL-PROPAN-2-ONE
627
MHz, [D6]DMSO): d 181.4, 144.4, 128.1, 126.5, 126.0, 59.7, (400 MHz): d 8.07(d, J 5 8.4 Hz, 1H), 7.83(d, J 5 8 Hz,
54.1, 52.1, 34.4, 31.3, 24.4, 24.3, 22.4. HRMS-ESI (m/z): 1H), 7.77(dd, J 5 2 Hz, 7.2 Hz, 1H), 7.40–7.59 (m, 2H),
calcd for C15H23N3S [M 1 H]1: 278.1685; found: 278.1688, 7.26–7.39 (m, 7H), 5.30 (dd, J 5 4.4 Hz, 12.8 Hz, 1H), 5.07
1.1 ppm.
(dd, J 5 7.6 Hz, 12.4 Hz, 1H), 4.87–4.93 (m, 1H), 4.28(d, J
5 10 Hz, 1H), 2.05 (s, 3H); 13C NMR (100 MHz): d 201.2,
133.2, 129.6, 129.0, 127.0, 126.2, 125.1, 124.1, 122.3, 78.2,
60.9, 37.6, 27.9. IR: 3064, 3008, 2920, 2852, 2254, 1711,
1555, 1513, 1478, 1377, 1357, 1255, 1219, 1093, 1024, 913,
1,10-[(1R,2R)-Cyclohexane-1,2-diyl]bis{3-[(R)-1-
phenylethyl]thiourea} 2f. [a]2D0 5 182(c 5 1.0, CH
Cl3); mp 181–1828C. 1H NMR (200 MHz, [D6]DMSO): d
7.88–7.92(d, J 5 8.4 Hz, 2H), 7.18–7.37 (m, 10H), 5.39–
5.46 (m, 2H), 4.11 (br, 2H), 1.99–2.07 (m, 2H), 1.59 (m,
2H), 1.38–1.41 (d, J 5 6.9 Hz, 6H), 1.18 (m, 4H); 13C
NMR (50 MHz, [D6]DMSO): d 181.1, 144.2, 128.2, 126.6,
126.1, 56.0, 52.3, 31.7, 23.9, 22.5. IR: 3439, 3069, 2929,
2250, 2124, 1998, 1772, 1655, 1546, 1228, 1056, 1028, 1008,
779, 744, 650 cm21
. HRMS-ESI (m/z): calcd for
C21H19NO3S 1NH41: 383.1424; found: 383.1429, 1.3 ppm.
Anal. Calcd for C21H19NO3S: C, 68.95; H, 5.24; N, 3.83.
Found: C, 68.65; H, 5.21; N, 3.81.
(3R,4S)-4-(Naphthalen-2-yl)-5-nitro-3-(phenylthio)-
pentan-2-one 4d. 63% yield, syn:anti 5 65:35, ee 5 96/
81%. [a]2D0 5 2121(c 5 1.8, CHCl3); mp 96–998C. ee was
determined by HPLC analysis (Chiralcel OD-H, iPrOH/
Hexane 5 30/70, 1.0 ml/min, syn: 225 nm, anti: 215 nm.)
Retention time: syn: tmajor 5 20.38 min, tminor 5 13.03 min,
ee 5 96%; anti: tmajor 5 17.72 min, tminor 5 15.98 min, ee
823, 761, 625 cm21
. HRMS-ESI (m/z): calcd for
C24H32N4S2 [M 1 H]1: 441.2141; found: 441.2144, 0.7
ppm.
(3R,4S)-5-Nitro-4-phenyl-3-(phenylthio)pentan-2-
one 4a. 58% yield, syn. anti 5 61:39, ee 5 89/90%.
[a]2D0 5 218 (c 5 0.7, CHCl3); mp 79–818C. ee was deter-
mined by HPLC analysis (Chiralcel OD-H, iPrOH/Hexane
5 20/80, 1.0 ml/min, 226 nm.) Retention time: syn: tmajor
1
5 81%. H NMR (400 MHz): d 7.73–7.77 (m, 3H), 7.63 (s,
1H), 7.36–7.46 (m, 7H),7.28 (d, J 5 8.4 Hz, 1H), 5.42 (dd, J
5 3.2 Hz, 16 Hz, 1H), 4.90 (dd, J 5 8.8 Hz, 11.6 Hz, 1H),
4.03–4.12 (m, 2H), 2.07 (s, 3H); 13C NMR (100 MHz): d
200.6, 134.0, 133.7, 133.2, 133.0, 131.1, 129.6, 129.3, 129.1,
127.9, 127.6, 127.5, 126.52, 126.47, 125.0, 78.8, 59.8, 44.0,
28.2. IR: 3061, 3022, 2924, 2854, 2254, 1714, 1556, 1509,
1477, 1377, 1356, 1245, 1024, 908, 735, 650 cm21. HRMS-
ESI (m/z): calcd for C21H19NO3S 1NH41: 383.1424; found:
383.1429, 1.3 ppm. Anal. Calcd for C21H19NO3S: C, 68.95;
H, 5.24; N, 3.83. Found: C, 68.73; H, 5.35; N, 3.42.
5 14.71 min, tminor 5 19.47 min, ee 5 89%; anti: tmajor
5
17.79 min, tminor 5 13.04 min, ee 5 90%. 1H NMR (400
MHz): d 7.40–7.44(m, 4H), 7.20–7.39 (m, 5H), 7.18 (d, J 5
6 Hz, 1H), 5.33 (dd, J 5 4 Hz, 12.8 Hz, 1H), 4.82 (dd, J 5
10 Hz, 12.8 Hz, 1H), 3.99 (d, J 5 11.6 Hz, 1H), 3.91 (dt, J
5 4 Hz, 10.8 Hz, 1H), 2.09 (s, 3H); 13C NMR (100 MHz):
d 200.8, 136.7, 133.4, 129.6, 129.1, 128.3, 127.9, 78.7, 59.9,
44.0, 28.1. IR: 3066, 3033, 2921, 2254, 1713, 1555, 1495,
1478, 1378, 1357, 1243, 1087, 913, 732, 650 cm21. HRMS-
ESI (m/z): calcd for C17H17NO3S 1NH41: 333.1267; found:
333.1267, 0.0 ppm. Anal. Calcd for C17H17NO3S: C, 64.68;
H, 5.39; N, 4.43. Found: C, 64.44; H, 5.32; N, 4.22.
(3R,4S)-4-(4-Methoxyphenyl)-5-nitro-3-(phenylthio)
pentan-2-one 4e. 68% yield, syn:anti 5 70:30, ee 5 82/
81%. [a]2D0 5 27 (c 5 0.9, CHCl3); mp 75–788C. ee was
determined by HPLC analysis (Chiralcel OD-H, iPrOH/
Hexane 5 3/97, 1.0 ml/min, 223 nm.) Retention time: syn:
tmajor 5 65.74 min, tminor 5 91.32 min, ee 5 82%; anti: tmajor
(3S,4S)-5-Nitro-4-phenyl-3-(p-tolylthio)pentan-2-
one 4b. 60% yield, syn. anti 5 35:65, ee 5 85/88%.
[a]2D0 5 132(c 5 1.0, CHCl3); mp 73–748C. ee was deter-
mined by HPLC analysis (Chiralcel AD-H, iPrOH/Hexane
5 10/90, 1.0 mL/min, 224 nm.) Retention time: syn: tmajor
1
5 65.74 min, tminor 5 51.02 min, ee 5 81%. H NMR (400
MHz): d 7.26–7.44(m, 5H), 7.10 (d, J 5 8.4 Hz, 2H), 6.81
(d, J 5 8.4 Hz, 2H), 5.31 (dd, J 5 4.4 Hz, 12.8 Hz, 1H),
4.76 (dd, J 5 9.6 Hz, 12.4 Hz, 1H), 3.96(d, J 5 11.2 Hz,
1H), 3.85 (dt, J 5 4 Hz, 11.2 Hz, 1H), 3.76 (s, 3H), 2.08 (s,
3H); 13C NMR (100 MHz): d 200.97, 159.4, 133.3, 129.6,
129.0, 128.3, 114.5, 78.9, 60.1, 55.2, 43.5, 27.96. IR: 3061,
3002, 2919, 2838, 2253, 1712, 1552, 1513, 1438, 1378, 1356,
1253, 1181, 1115, 1031, 912, 834, 744, 692 cm21. HRMS-
ESI (m/z): calcd for C18H19NO4S 1NH41: 368.1373; found:
368.1376, 0.8 ppm. Anal. Calcd for C18H19NO4S: C, 62.67;
H, 5.56; N, 4.05. Found: C, 63.07; H, 5.50; N, 3.87.
5 10.82 min, tminor 5 14.01 min, ee 5 85%; anti: tmajor
5
7.31 min, tminor 5 8.31 min, ee 5 88%. 1H NMR (400
MHz): d 7.24–7.34 (m, 3H), 7.08–7.15 (m, 6H), 4.87 (dd, J
5 8.4 Hz, 12.8 Hz, 1H), 4.75 (d, J 5 12.8 Hz, 1H), 4.06 (d,
J 5 9.2 Hz, 1H), 3.69 (m, 1H), 2.33 (s, 6H); 13C NMR (100
MHz): d 203.3, 139.7, 136.6, 134.7, 130.1, 129.0, 128.3,
128.1, 127.3, 77.8, 59.5, 44.3, 29.5, 21.2. IR: 3154, 3031,
2982, 2923, 2254, 1706, 1553, 1493, 1379, 1358, 1216, 1095,
908, 733, 650, 624 cm21. HRMS-ESI (m/z): calcd for
C18H19NO3S 1NH41: 347.1424; found: 347.1424, 0.0 ppm.
Anal. Calcd for C18H19NO3S: C, 64.33; H, 6.03; N, 4.41.
Found: C, 64.60; H, 5.72; N, 4.27.
(3R,4S)-4-(2-Methoxyphenyl)-5-nitro-3-(phenylthio)
pentan-2-one 4f. 63% yield, syn:anti 5 60:40, ee 5 92/
90%. [a]2D0 5 217 (c 5 0.5, CHCl3); mp 101–1048C. ee was
(3R,4S)-4-(Naphthalen-1-yl)-5-nitro-3-(phenylthio)- determined by HPLC analysis (Chiralcel AD-H, iPrOH/
pentan-2-one 4c. 54% yield, syn:anti 5 68:32, ee 5 92/ Hexane 5 2/98, 0.6 ml/min, 219 nm.) Retention time: syn:
90%. [a]2D0 5 224 (c 5 0.8, CHCl3); mp 130–1328C. ee was tmajor 5 40.20 min, tminor 5 42.68 min, ee 5 92%; anti: tmajor
1
determined by HPLC analysis (Chiralcel OD-H, iPrOH/ 5 25.81 min, tminor 5 28.17 min, ee 5 90%. H NMR (400
Hexane 5 30/70, 0.5 mL/min, 226 nm.) Retention time: MHz): d 7.20–7.44 (m, 6H), 7.08 (dd, J 5 1.6 Hz, 8 Hz,
syn: tmajor 5 33.93 min, tminor 5 30.25 min, ee 5 92%; anti: 1H), 6.83–6.87(m, 2H), 5.23 (dd, J 5 4.4 Hz, 12.8 Hz, 1H),
1
tmajor 5 25.94 min, tminor 5 20.30 min, ee 5 90%. H NMR 5.07 (dd, J 5 9.2 Hz, 12.4 Hz, 1H), 4.35 (d, J 5 11.6 Hz,
Chirality DOI 10.1002/chir

628
JIANG ET AL.
1H),4.05 (dt, J 5 2 Hz, 4 Hz, 1H), 3.82 (s, 3H), 2.09 (s, 202.9, 138.97, 134.1, 131.5, 130.5, 129.4, 129.3, 126.9, 123.0,
3H); 13C NMR (100 MHz): d 201.3, 156.9, 132.95, 131.9, 77.5, 59.4, 44.3, 29.3. IR: 3155, 3064, 2922, 2852, 2254,
131.1, 129.6, 129.4, 128.7, 123.8, 121.1, 111.3, 76.6, 58.2, 1709, 1556, 1477, 1377, 1358, 1216, 1096, 912, 743, 651
55.4, 41.5, 27.5. IR: 3068, 3008, 2926, 2845, 2255, 1711, cm21. HRMS-EI (m/z): calcd for C17H16BrNO3S: 393.0029;
1553, 1466, 1436, 1378, 1357, 1247, 1173, 1121, 1026, 917, found: 393.0025, 1.0 ppm. Anal. Calcd for C17H16BrNO3S:
757, 651 cm21. HRMS-ESI (m/z): calcd for C18H19NO4S C, 51.74; H, 4.01; N, 3.55. Found: C, 51.65; H, 3.70; N,
1Na: 368.0927; found: 368.0928, 0.3 ppm. Anal. Calcd for 3.47.
C18H19NO4S: C, 62.67; H, 5.56; N, 4.05. Found: C, 62.51;
H, 5.92; N, 4.07.
(3S,4S)-4-(4-Chlorophenyl)-5-nitro-3-(phenylthio)-
pentan-2-one 4j. 51% yield, syn:anti 5 30:70, ee 5 81/
(3S,4S)-4-(4-Fluorophenyl)-5-nitro-3-(phenylthio)- 78%. [a]2D0 5 174(c 5 1.1, CHCl3); mp 109–1108C. ee was
pentan-2-one 4g. 61% yield, syn:anti 5 20:80, ee 5 84/ determined by HPLC analysis (Chiralcel OD-H, iPrOH/
90%. [a]2D0 5 1105(c 5 0.9, CHCl3); mp 89–908C. ee was Hexane 5 30/70, 0.4 ml/min, syn: 221 nm, anti: 219 nm.)
determined by HPLC analysis (Chiralcel AD-H, iPrOH/ Retention time: syn: tmajor 5 21.66 min, tminor 5 30.17 min,
Hexane 5 10/90, 1.0 ml/min, 210 nm.) Retention time: ee 5 81%; anti: tmajor 5 25.69 min, tminor 5 23.92 min, ee
syn: tmajor 5 14.09 min, tminor 5 17.16 min, ee 5 84%; anti: 5 78%. 1H NMR (400 MHz): d 7.31–7.37 (m, 5H), 7.23–
tmajor 5 8.09 min, tminor 5 9.40 min, ee 5 90%. 1H NMR 7.26 (m, 2H), 7.08 (d, J 5 8.4 Hz, 2H), 4.86 (dd, J 5 8 Hz,
(400 MHz): d 7.23–7.39 (m, 5H), 7.11–7.15 (m, 2H), 7.01– 12.4 Hz, 1H), 4.74 (dd, J 5 3.2 Hz, 12.4 Hz, 1H), 4.08 (d, J
7.06 (m, 2H), 4.86 (dd, J 5 8 Hz, 12.4 Hz, 1H), 4.74 (dd, J 5 9.6 Hz, 1H), 3.73–3.76 (m, 1H), 2.38 (s, 3H); 13C NMR
5 4 Hz, 12.8 Hz, 1H), 4.08 (d, J 5 9.2 Hz, 1H), 3.74–3.78 (100 MHz) anti: d 203.0, 135.1, 134.3, 134.02, 131.2, 129.6,
(m, 1H), 2.37 (s, 3H); 13C NMR (100 MHz): d 203.2, 129.4, 129.3, 129.2, 77.6, 59.4, 44.0, 29.3. syn: 200.4, 135.4,
134.1, 132.2, 131.1, 129.9, 129.86, 129.4, 129.3, 116.1, 115.9, 134.3, 133.7, 129.7, 129.3, 78.5, 59.6, 43.3, 28.4. IR: 3154,
77.8, 59.5, 44.8, 29.4. IR: 3069, 3017, 2970, 2922, 2851, 3064, 2984, 2920, 2852, 2254, 1708, 1553, 1437, 1378, 1216,
2377, 1700, 1561, 1510, 1439, 1379, 1353, 1223, 1158, 1099, 1095, 1015, 913, 743, 651, 623 cm21. HRMS-ESI (m/z):
1
1024, 918, 833, 750, 691 cm21. HRMS-ESI (m/z): calcd for calcd for C17H16ClNO3S 1NH4
:
367.0878; found:
C17H16FNO3S 1NH41: 351.1173; found: 351.1174, 0.3 367.0880, 0.5 ppm. Anal. Calcd for C17H16ClNO3S: C,
ppm. Anal. Calcd for C17H16FNO3S: C, 61.19; H, 4.79; N, 58.37; H, 4.61; N, 4.00. Found: C, 58.75; H, 4.93; N, 4.00.
4.19. Found: C, 60.92; H, 4.69; N, 4.10.
(3S,4S)-5-Nitro-4-(4-nitrophenyl)-3-(phenyl thio)-
(3S,4S)-4-(4-Bromophenyl)-5-nitro-3-(phenylthio) pentan-2-one 4k. 71% yield, syn:anti 5 43:57, ee 5 75/
pentan-2-one 4h. 56% yield, syn. anti 5 25:75, ee 5 57%. [a]2D0 5 17(c 5 1.0, CHCl3); mp 126-1288C. ee was
83/76%. [a]2D0 5 162(c 5 0.75, CHCl3); mp 98–1008C. ee determined by HPLC analysis (Chiralcel AD-H, iPrOH/
was determined by HPLC analysis (Chiralcel OD-H, Hexane 5 10/90, 1.0 ml/min, 219 nm.) Retention time:
iPrOH/Hexane 5 30/70, 0.8 ml/min, syn:222 nm, anti: syn: tmajor 5 21.50 min, tminor 5 31.15 min, ee 5 75%; anti:
1
219 nm.) Retention time: syn: tmajor 5 12.65 min, tminor
18.36 min, ee 5 83%; anti: tmajor 5 16.10 min, tminor
5
5
tmajor 5 36.07 min, tminor 5 77.08 min, ee 5 86%. H NMR
(400 MHz): d 8.19(d, J 5 8.8 Hz, 2H), 7.26–7.41 (m, 5H),
14.07 min, ee 5 76%. 1H NMR (400 MHz): d 7.44 (d, J 5 7.19 (d, J 5 1.6 Hz, 2H), 4.89 (dd, J 5 8 Hz, 13.2 Hz, 1H),
8.4 Hz, 2H), 7.27–7.40 (m, 3H), 7.04–7.24 (m, 2H), 7.01 (d, 4.74 (dd, J 5 4 Hz, 12.8 Hz, 1H), 4.15 (d, J 5 9.6 Hz, 1H),
J 5 8 Hz, 2H), 4.84 (dd, J 5 7.6 Hz, 12.4 Hz, 1H), 4.72 (dd, 3.85–3.90 (m, 1H), 2.43 (s, 3H); 13C NMR (100 MHz): d
J 5 4 Hz, 12.8 Hz, 1H), 4.06 (d, J 5 9.2 Hz, 1H), 3.67–3.73 202.4, 147.8, 143.99, 134.0, 130.6, 129.8, 129.53, 129.45,
(m, 1H), 2.36 (s, 3H); 13C NMR (100 MHz): d 203.03, 124.1, 58.7, 44.2, 29.2. IR: 3078, 2920, 2853, 1707, 1603,
135.5, 134.2, 132.2, 130.9, 129.9, 129.39, 129.36, 122.3, 77.6, 1553, 1520, 1436, 1377, 1348, 1244, 1112, 1019, 856, 749,
59.1, 43.9, 29.4. IR: 3061, 3007, 2945, 2919, 1907, 1699, 695, 657 cm21. HRMS-ESI (m/z): calcd for C17H16N2O5S
1550, 1488, 1439, 1376, 1360, 1246, 1074, 1012, 916, 819, 1Na: 383.0672; found: 383.0666, 1.6 ppm. Anal. Calcd for
747, 691, 649, 574 cm21. HRMS-EI (m/z): calcd for C17H16N2O5S: C, 56.60; H, 4.47; N, 7.77. Found: C, 56.97;
C17H16BrNO3S: 393.0029; found: 393.0026, 0.8 ppm. Anal. H, 4.61; N, 7.55.
Calcd for C17H16BrNO3S: C, 51.74; H, 4.01; N, 3.55. Found:
C, 51.75; H, 3.66; N, 3.45.
(3S,4S)-4-(Furan-2-yl)-5-nitro-3-(phenylthio)pentan-
2-one 4l. 65% yield, syn. anti 5 40:60, ee 5 86/84%.
(3S,4S)-4-(3-Bromophenyl)-5-nitro-3-(phenylthio) [a]2D0 5 156(c 5 1.3, CHCl3); mp 77–808C. ee was deter-
pentan-2-one 4i. 62% yield, syn. anti 5 27:73, ee 5 mined by HPLC analysis (Chiralcel OD-H, iPrOH/Hexane
84/76%. [a]2D0 5 120(c 5 0.6, CHCl3); mp 70–738C. ee was 5 10/90, 0.6 ml/min, 216 nm.) Retention time: syn: tmajor
determined by HPLC analysis (Chiralcel AD-H, iPrOH/ 5 29.23min, tminor 5 42.42 min, ee 5 86%; anti: tmajor
5
Hexane 5 5/95, 0.8 ml/min, syn: 220 nm, anti: 210 nm.) 36.02 min, tminor 5 27.95 min, ee 5 84%. 1H NMR (300
Retention time: syn: tmajor 5 19.07 min, tminor 5 22.34 min, MHz): d 7.26–7.37 (m, 6H), 6.35 (dd, J 5 2.7 Hz, 4.8 Hz,
ee 5 84%; anti: tmajor 5 13.31 min, tminor 5 13.99 min, ee 1H), 6.25 (d, J 5 5.1 Hz, 1H), 4.73–4.88 (m, 2H), 4.23 (d, J
5 76%. 1H NMR (400 MHz): d 7.45 (d, J 5 8 Hz, 1H), 5 13.2 Hz, 1H), 3.86–3.96 (m, 1H), 2.36 (s, 3H); 13C NMR
7.30–7.41 (m, 2H), 7.13–7.27 (m, 5H), 7.09 (d, J 5 7.2 Hz, (75 MHz): d 202.5, 150.1, 142.5, 134.2, 129.4, 129.2, 110.6,
1H), 4.86 (dd, J 5 7.6 Hz, 12.4 Hz, 1H), 4.74 (dd, J 5 3.6 109.0, 76.1, 57.9, 38.6, 29.1. IR: 3122, 3060, 3020, 2921,
Hz, 12.4 Hz, 1H), 4.08 (d, J 5 8.8 Hz, 1H), 3.72 (dt, J 5 4 1708, 1555, 1476, 1439, 1377, 1358, 1148, 1071, 1015, 917,
Hz, 8.4 Hz, 1H), 2.38 (s, 3H); 13C NMR (100 MHz): d 814, 745, 692 cm21
. HRMS-ESI (m/z): calcd for
Chirality DOI 10.1002/chir

MICHAEL ADDITION OF ARYL SULFANYL-PROPAN-2-ONE
629
TABLE 1. Results of exploratory studies on the catalytic
asymmetric Michael addition reaction of phenyl
sulfanyl-propan-2-one (3a) to nitroalkene (1a)a
Time Yield
[h]
Dr
ee
Entry Catalyst Solvent
(%)b
(syn/anti)c (%)d
1
2
3
2a
2b
2c
2d
2e
2f
2d
2d
2d
2d
Tol
Tol
Tol
Tol
Tol
72
72
72
72
72
72
24
72
72
72
trace
trace
trace
50
46
trace
40
15
<10
40
n.d
n.d
n.d
60/40
45/55
n.d
50/50
50/50
n.d
n.d
n.d
n.d
81
70
n.d
35
46
n.d
72
4
5e
6
Tol
7
8
9
10
MeOH
DMSO
THF
CH2Cl2
56/44
aThe reaction was conducted with 1a (3.0 equiv.), 3a (1.0 equiv.).
bIsolated yields.
cDetermined by 400 Hz 1H NMR.
Fig. 1. Structures of chiral orgnaocatalysts.
dRelative and absolute configurations were determined by X-ray crystal
data of 4a and the ee values (syn) were determined by chiral HPLC.
eRelative and absolute configurations were based on the comparison of
the optical rotation, X-ray crystal data of 4a, chiral HPLC analysis and the
ee value (anti) was determined by chiral HPLC.
C15H15NO4S 1NH41: 323.1060; found: 323.1065, 1.5 ppm.
Anal. Calcd for C15H15NO4S: C, 59.00; H, 4.95; N, 4.59.
Found: C, 58.93; H, 4.99; N, 4.20.
(3S,4S)-5-Methyl-4-(nitromethyl)-3-(phenylthio)hexan- 10.74 min, ee 5 88%. 1H NMR (300 MHz): d 7.32–7.42 (m,
2-one 4m. 36% yield, syn. anti 5 36:64, ee 5 88/97%. 5H), 4.81–4.87 (dd, J 5 4.5 Hz, 14.1 Hz, 1H), 4.54–4.61
[a]2D0 5 16(c 5 0.8, CHCl3). ee was determined by HPLC (dd, J 5 6.3 Hz, 14.1 Hz, 1H), 3.72 (d, J 5 10.2 Hz, 1H),
analysis (Chiralcel OD-H, iPrOH/Hexane 5 10/90, 1.0 2.84–2.99 (m, 1H), 2.32 (s, 3H), 1.82–1.88 (m, 1H), 0.97 (d,
ml/min, 216 nm.) Retention time: anti: tmajor 5 7.91min, J 5 7.2 Hz, 3H), 0.86 (d, J 5 6.9 Hz, 3H); 13C NMR (75
tminor 5 7.59 min, ee 5 97%; syn: tmajor 5 8.63 min, tminor
5
MHz): d 203.4 132.8, 132.3, 129.5, 128.7, 74.2, 60.1, 42.5,
TABLE 2. Results for optimizing the reaction conditionsa
Entry
Additive (equiv.)
Time [h]b
Yield (%)c
Dr (syn/anti)d
ee (%)e
1
2
3
4
5
6
7
8
9
PhCOOH (0.15)
PhCOOH (0.30)
PhCOOH (1.0)
72
72
72
5d
5d
5d
72
72
72
58
56
45
trace
trace
trace
30
61/39
61/39
n.d
n.d
n.d
n.d
n.d
58/42
60/40
89
88
n.d
n.d
n.d
n.d
n.d
87
p-TSOH.H2O (0.15)
TFA (0.15)
TFA (0.15), H2O (2.0)
AcOH (0.15)
AcOH (0.15), H2O (2.0)
AcOH (0.15), H2O (3.0)
56
50
87
aThe reaction was conducted with 1a (3.0 equiv), 3a (1.0 equiv.) in toluene.
bThe resulting mixture was stirred for 2 h at 08C and then stirred at 208C.
cIsolated yields.
dDetermined by 400 Hz 1H NMR.
eRelative and absolute configurations were determined by X-ray crystal data of 4a and the ee values (syn) were determined by chiral HPLC.
Chirality DOI 10.1002/chir

630
JIANG ET AL.
TABLE 3. Asymmetric addition of aryl
TABLE 3. (Continued)
sulfanyl-propan-2-one to nitroalkenes by 2d.a,b
Yield
(%)c
Dr
ee %
Entry
Product
(syn/anti)d
(syn/anti)e
11
4k: 71
4l: 65
43/57
75/86
86/84
88/97
Yield
(%)c
Dr
ee %
Entry
1
Product
(syn/anti)d
(syn/anti)e
4a: 58
61/39
89/90
12
40/60
13
4m: 36
36/64
2
4b: 60
4c: 54
4d: 63
4e: 68
4f: 63
4g: 61
4h: 56
4i: 62
4j: 51
35/65
68/32
65/35
70/30
60/40
20/80
25/75
27/73
30/70
85/88
92/90
96/81
82/81
92/90
84/90
83/76
84/76
81/78
aIn all of the entries: phenyl thioethers: nitroalkenes: PhCOOH 5 1:3:0.15.
bThe resulting mixture was stirred for 2 h at 0 8C, then was stirred at
208C.
cIsolated yields after purification by column chromatography on silica gel.
dDetermined by 400Hz 1H NMR.
3
eThe ee values were determined by chiral HPLC, relative and absolute
configurations were determined by X-ray crystal data of 4a, chiral HPLC
analysis and comparison with known literatures.49
4
29.2, 27.5, 20.7, 17.0. IR: 3065, 3020, 2921, 2254, 1718,
1555, 1480, 1378, 1361, 1087, 913, 742, 641 cm21. HRMS-
EI (m/z): calcd for C14H19NO3S: 281.1080; found:
281.1081, 0.4 ppm.
5
(3S,4S)-5-Nitro-4-phenyl-3-(phenylsulfonyl)pentan-
2-one 5a. 83% yield. [a]2D0 5 136(c 5 0.8, CHCl3); mp
156–1588C. 1H NMR (400 MHz): d 7.66–7.74 (m, 3H),
7.51–7.55 (m, 2H), 7.19–7.26 (m, 4H), 6.95–6.97 (m, 1H),
4.99–5.01 (m, 2H), 4.70 (d, J 5 6.4 Hz, 1H), 4.12-4.17 (m,
1H), 2.31 (s, 3H); 13C NMR (100 MHz): d 199.7, 137.9,
135.6, 135.1, 134.6, 129.5, 129.4, 128.8, 128.2(syn), 127.6,
76.5, 76.3, 42.4, 34.1. IR: 3155, 2924, 2253, 1794, 1722,
6
1556, 1380, 1257, 1149, 1083, 908, 734, 651, 613, 542 cm21
.
7
HRMS-EI (m/z): calcd for C17H17NO5S-C6H5O2S:
206.0812; found: 206.0813, 0.5 ppm. Anal. Calcd for
C17H17NO5S: C, 58.78; H, 4.93; N, 4.03. Found: C, 59.12;
H, 4.53; N, 3.66.
8
RESULTS AND DISCUSSION
We began our studies by screening several chiral orga-
nocatalysts for their ability to promote asymmetric Mi-
chael addition reactions of phenyl sulfanyl-propan-2-one 3a
to nitroalkene 1a (Fig. 1 and Table 1). Initially, several
readily accessible L-proline derivatives32–53 2a–2c (see
Fig. 1) as the organocatalysts were screened. Surprisingly,
no reactions occurred after 72 h in toluene (entries 1–3,
Table 1). Hence, the amine-thiourea based organocata-
lysts54–83 2d–2f (see Fig. 1) was examined. Gratifyingly,
the chiral amine-thioureas 2d and 2e were observed to be
effective promoters for asymmetric conjugate addition of
9
10
Chirality DOI 10.1002/chir

MICHAEL ADDITION OF ARYL SULFANYL-PROPAN-2-ONE
631
Fig. 3. The X-ray crystal structure of 4a: (3R,4S)-5-nitro-4-phenyl-3-
(phenylthio) pentan-2-one (The CCDC deposition number: CCDC
686821.).
Fig. 2. The proposed catalytic cycle.
isopropyl substituted nitroalkene with a low yield of 36%
(entries 3, 4, 12, and 13, Table 3).
phenyl sulfanyl-propan-2-one 3a to nitroalkene 1a. Espe-
cially, the adduct 4a was obtained in 50% yield and 81% ee
in the presence of 15 mol % of 2d in toluene (entry 4, Ta-
ble 1). Encouraged by the results, several solvents such as
MeOH, DMSO, THF, CH2Cl2 were screened with thiourea
2d. The reaction of nitroalkene 1a with 3a in the pres-
ence of 15 mol % of 2d in methanol afforded the desired
Michael adduct 4a in 40% yield and 35% ee (entry 7, Table
1). Therefore, other solvents were examined. The polar
solvents (DMSO, THF), which reduced the catalytic activ-
ity of 2d, resulted in poor yields (entries 8 and 9, Table 1).
In contrast, 2d efficiently promoted the reaction in nonpo-
lar solvent (CH2Cl2) with a high enantioselectivity of 72%
ee but a low yield of 40% (entry 10, Table 1).
We also found that the addition of a small amount of a
Bronsted acid could lead to further improvement of the
yield and enantioselectivity. Therefore, several Bronsted
acid additives were screened (Table 2). To our delight,
performing the asymmetric conjugate additions in the
presence of a small amount of acetic acid (with 2-3 equiv.
of H2O) or benzoic acid markedly increased the yields and
enantioselectivities of the reaction (entries 1, 2, 8, and 9,
Table 2). Especially, under the optimized condition (entry
1, Table 2), the chiral primary amine-thiourea 2d medi-
ated the asymmetric assembly of 4a in up to 58% yield
with up to 89% ee in the presence of benzoic acid (0.15
equiv.).
Under the optimized reaction condition, the asymmetric
additions of aryl sulfanyl-propan-2-one to nitroalkenes 1a–
1l afforded the corresponding adducts in moderate to
good yields with up to 97% ee and 20:80 dr (syn:anti). The
results are summarized in Table 3. The addition of aryl sul-
fanyl-propan-2-one to a variety of nitroalkenes obtained the
desired products with good enantioselectivity when aro-
matic nitroalkenes have either electron donating or elec-
tron withdrawing substituents under the optimized condi-
tion (entries 5–11, Table 3). As expected, 1-naphthyl, 2-
naphthyl, 2-furyl, and isopropyl substituted nitroalkenes
were also suitable substrates as Michael acceptors, high
enantioselectivities were still obtained but the reaction of
The proposed possible mechanism is shown in Figure
2. The primary amine-thiourea bifunctional catalytic mech-
anism involving the process of enamine intermediate has
been described.67,74 In our catalytic system, we obtained
syn or anti major adducts for different Michael donors and
acceptors. This phenomenon might be attributed to effec-
tive formation of the corresponding E-enamine or Z-enam-
ine intermediate.
The relative and absolute configurations of the adduct
4a were determined by X-ray diffraction (see Fig. 3). It
may be considered that the configurations of adducts 4c–
4f are the same and the configurations of other adducts
4b, 4g–4l were deduced by the configuration of the pro-
duct 4a and comparison with known literatures49,67
In our work, although we obtained the highly functional-
ized adducts with high enantioselectivities, diastereoselec-
tivities are moderate so that the application of these highly
functionalized adducts may be reduced in organic synthe-
sis. Fortunately, we obtained sole anti-diastereoselective
oxidated products by the further transformation of the
adducts. In Scheme 1, the asymmetric adduct 4a (syn/
anti: 61:39) was oxidized by m-CPBA (2 equiv.) in CH2Cl2
and then, oxidized product was added to a toluene solution
of LiHMDS (2.5 equiv.) at 2788C. To our delight, we
obtained sole anti-diastereoselective oxidated product 5a
with 83% yield of two steps. This configuration reversal
Scheme 1. The procedure for the adducts were transformed.
Chirality DOI 10.1002/chir

632
JIANG ET AL.
10. Feldman KS. Modern Pummerer-type reactions. Tetrahedron
2006;62:5003–5034.
might due to the effect of a sterically-hindered lithium am-
ide base (lithium bis(trimethylsilyl)amide). The sensitivity
of the diastereoselectivity to steric bulk is in sharp in this
process. In transition state, because of the necessity for
energy minimization of steric interactions between 4a and
the sterically-hindered lithium amide base, the facial si-se-
lectivity of 4a is governed in favor of the anti-transition
structure. In addition, other organic bases such as n-butyl-
lithium and lithium diisopropylamide were also investi-
gated. Under the above reaction condition, although the
sterically hindered lithium diisopropylamide (2.5 equiv.)
could also promote the formation of anti-diastereoselective
5a (anti/syn: 78:22), the sole anti-diastereoselective oxi-
dated product could not be obtained in the presence of n-
butyllithium or Lithium diisopropylamide. This represen-
tative example demonstrates the inherent synthetic
potential of this methodology. As far as know, the applica-
tion of the effect of such sterically-hindered base in the
configuration reversal of the chiral compounds is much
less developed, further studies are under investigated in
our laboratory.
11. Bur SK, Padwa A. The pummerer reaction: methodology and strategy
for the synthesis of heterocyclic compounds. Chem Rev 2004;104:
2401–2432.
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thesis of the cephalotaxus alkaloids dl-cephalotaxine, dl-11-hydroxyce-
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deficient olefins: b-phenylthio nitro olefins, b-sulfinyl nitro olefins,
and b-sulfonyl nitro olefins. J Org Chem 1986;51:2139–2142.
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Asymmetric conjugate reduction of a,b-unsaturated esters using a chi-
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CONCLUSION
In summary, our studies revealed that chiral primary
amine-thiourea were suitable catalysts for the asymmetric
Michael addition of thioether-based aryl sulfanyl-propan-2-
one to a number of nitroalkenes, affording the highly func-
tionalized adducts with excellent enantioselectivities. Espe-
cially, the configuration reversal might take place when
the further oxidated products were treated with LiHMDS,
providing sole anti-diastereoselective products. Given the
synthetic and biological versatility of thioethers, these
highly functionalized chiral adducts could play an important
role in organic synthesis and biochemical utility. Further
studies of these chiral adduct in organic synthesis and bio-
chemical utility is currently going on in our laboratory.
20. Sakya SM, Slrohmeyef TW, Lang SA, Lin Y. Preparation of novel tricy-
clic diazo carbapenems: application of inverse electron demand diels-
alder reactions of 3,6-bis(methylthio)-1,2,4,5-tetrazine. Tetrahedron
Lett 1997;38:5913–5916.
21. Basak A, IfhAmrai UK. Design, synthesis and biological activity of
novel enediynyl monocyclic b-lactams. Tetrahedron Lett 1996;37:
2475–2478.
22. Gamble MP, Giblin GMP, Taylor ,RJK. Amino acid derived sulfones
for chiral cyclopentane synthesis. Synlett 1995;779–780.
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