Synthesis of sulfur-substituted α-stereogenic amides and ketones: Highly enantioselective sulfa-michael additions of 1,4-dicarbonylbut-2-enes

Article abstract of DOI:10.1002/adsc.201100227

Conjugate addition to 1,4-dicarbonylbut-2-enes will generate an α-stereogenic center with respect to one of the carbonyl groups, which informally, can be considered as an inversion of normal reactivity patterns or umpolung protocol. In this paper, the add

Full text of DOI:10.1002/adsc.201100227

COMMUNICATIONS
DOI: 10.1002/adsc.201100227
Synthesis of Sulfur-Substituted a-Stereogenic Amides and
Ketones: Highly Enantioselective Sulfa-Michael Additions of
1,4-Dicarbonylbut-2-enes
Fangli Zhao,a,b,d Wen Zhang,b,d Yuanyong Yang,c Yuanhang Pan,c
Wenchao Chen,a,b Hongjun Liu,c Lin Yan,a,b,* Choon-Hong Tan,b,c,*
and Zhiyong Jianga,b,*
a
Institute of Chemical Biology, Henan University, Kaifeng, Henan 475004, Peopleꢀs Republic of China
Key Laboratory of Natural Medicine and Immuno-Engineering of Henan Province, Henan University, Kaifeng, Henan,
b
475004, Peopleꢀs Republic of China
E-mail: yanlin@henu.edu.cn or chmjzy@henu.edu.cn
Department of Chemistry, National University of Singapore, 3 Science Drive 3, Singapore 117543
c
E-mail: chmtanch@nus.edu.sg
F. Zhao and W. Zhang made equal contributions to this work.
d
Received: March 29, 2011; Revised: June 6, 2011; Published online: October 10, 2011
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/adcs.201100227.
Abstract: Conjugate addition to 1,4-dicarbonylbut-
2-enes will generate an a-stereogenic center with
respect to one of the carbonyl groups, which infor-
mally, can be considered as an inversion of normal
reactivity patterns or umpolung protocol. In this
paper, the addition of tert-butyl mercaptan to 1,4-di-
carbonylbut-2-enes including (E)-4-oxo-4-arylbut-
resulted in the formation of sulfides bearing a stereo-
genic center b to an electron-withdrawing group since
the b-carbon often behaves as an electrophile center.
Enantioselective protonation of an enolate, gener-
ated from the conjugate addition of thiols to activated
terminal alkenes, has been demonstrated to be highly
desirable to construct a-stereogenic sulfides,[6n,p,r] how-
ever, the sulfur atom is not embedded to the stereo-
genic center. Recently, Xiao et al have developed an
asymmetric sulfa-Michael addition of aromatic thiols
to b,b-disubstituted nitroalkenes to access chiral b2,2-
amino acids, which produced the sulfur-substituted a-
stereogenic esters.[6m] By introducing an electron-with-
drawing nitro group at the b-position of acrylate, the
reactivity of its a-carbon is inversed from a nucleo-
phile to an electrophile. Therefore, this could infor-
mally be considered as an inversion of normal reactiv-
ity patterns or umpolung reactivity.[7]
ACHTUNGTRENNUNGenamides and (E)-4-oxo-4-arylbutenones has been
developed, to synthesize a series of chiral sulfur-
substituted a-stereogenic amides and ketones in
high regioselectivity and enantioselectivity (up to
98% ee).
Keywords: asymmetric catalysis; 1,4-dicarbonylbut-
2-enes; organocatalysis; a-stereogenic amides and
ketones; sulfa-Michael addition
Since both amides and ketones with a-stereogenic
centers are useful building blocks for the synthesis of
Molecules with sulfur-containing frameworks are biologically active compounds,[8] the asymmetric syn-
common key building blocks in pharmaceutical and thesis of them has been attractive to chemists.[9] We
natural products.[1] Many chiral sulfur-containing com- have developed a highly enantio- and regioselective
pounds have become useful ligands,[2] organocata- protocol to construct carbon-substituted a-stereogenic
lysts,[3] and chiral reagents or auxiliaries.[4] The asym- amides and ketones[9a] during our investigations of
metric Michael addition of thiols to activated alkenes chiral bicyclic guanidine-catalyzed reactions.[6n,p,9a,10]
enables an efficient construction of valuable optically The acceptors were designated as 1,4-dicarbonylbut-2-
active sulfur-containing compounds.[5] Both asymmet- enes including (E)-4-oxo-4-arylbutenamides and (E)-
ric organometallic and organocatalytic approaches for 4-oxo-4-arylbutenones; using a similar umpolung con-
sulfa-Michael additions have been extensively studied cept to generate a-stereogenic amides and ketones. It
by several research groups.[6] However, most of them is noteworthy that sulfur-substituted a-stereogenic ke-
2624
ꢁ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2011, 353, 2624 – 2630

Synthesis of Sulfur-Substituted a-Stereogenic Amides and Ketones
Figure 1. Structures of various bifunctional organocatalysts I–VI.
tones as side products were detected in high regiose- factory results were obtained under the same condi-
lectivities but poor enantioselectivities [Eq. (1)]. tions when other thiols 1b–d were used as donors and
Thus, we are keen to develop a highly enantio- and (E)-4-oxo-4-arylbutenamides with different amide
regioselective synthesis of sulfur-substituted a-stereo- moieties 2b–e were employed as acceptors (Table 1,
genic amides and ketones via the sulfa-Michael addi- entries 7–13). In combination with IV as the opti-
tion between thiols and 1,4-dicarbonylbut-2-enes [Eq. mized organocatalyst, 1a and 2a were chosen as
(2)].
model substrates for further optimization. Lowering
In our exploratory studies, tert-butyl mercaptan the temperature to À208C effected an improvement
(TBM) 1a was subjected to Michael conjugation with of the enantioselectivity (Table 1, entry 14). A screen
(E)-4-oxo-4-arylbutenamide 2a catalyzed using of different solvents revealed that dichloromethane
10 mol% guanidine I (Figure 1) in toluene at 08C was the best reaction medium (Table 1, entries 15–
(Table 1, entry 1). We found that the reaction pro- 17). Finally, 3aa could be obtained in high yield and
ceeded efficiently to afford the adduct 3aa in excel- in 92% ee in dichloromethane at À508C (Table 1, en-
lent yield but moderate enantioselectivity (56% ee). tries 18 and 19). The reaction rate was increased
Further investigation did not improve the enantiose- about twice without compromising the enantio- and
lectivity. Therefore, we tested other bifunctional cata- regioselectivity by increasing the amount of 1a from
lysts II–VI (Figure 1) derived from Cinchona alka- 3.0 to 5.0 equivalents. With the optimized reaction
loids (Table 1, entries 2–6).[11] The highest enantiose- conditions, 1c and 1d as donors were tested with ac-
lectivity (78% ee) of 3aa was achieved in the presence ceptor 2a. However, the enantioselectivities were not
of 10 mol% IV as catalyst (Table 1, entry 4). Unsatis- improved (Table 1, entries 20 and 21). The reaction
Adv. Synth. Catal. 2011, 353, 2624 – 2630
ꢁ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
2625

Fangli Zhao et al.
COMMUNICATIONS
Table 1. Asymmetric addition of thiols 1a–d to (E)-4-oxo-4-arylbutenamides 2a–d catalyzed by different bifunctional organo-
catalysts I–VI.[a]
Entry
1
2
Catalyst
Solvent
T [oC]
t [h]
3
Yield [%][b]
ee [%][c]
1
2
3
4
5
6
7
8
1a [tert-butyl]
1a [tert-butyl]
1a [tert-butyl]
1a [tert-butyl]
1a [tert-butyl]
1a [tert-butyl]
1b [n-propyl]
1c [isopropyl]
1d [Bn]
1a [tert-butyl]
1a [tert-butyl]
1a [tert-butyl]
1a [tert-butyl]
1a [tert-butyl]
1a [tert-butyl]
1a [tert-butyl]
1a [tert-butyl]
1a [tert-butyl]
1a [tert-butyl]
1c [isopropyl]
1d [Bn]
2a
2a
2a
2a
2a
2a
2a
2a
2a
2b
2c
2d
2e
2a
2a
2a
2a
2a
2a
2a
2a
2a
I
II
III
IV
V
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
CH2Cl2
CHCl3
0
0
0
0
0
0
0
0
0
0
0
0
0.5
48
48
48
48
48
9
3aa
3aa
3aa
3aa
3aa
3aa
3ba
3ca
3da
3ab
3ac
3ad
3ae
3aa
3aa
3aa
3aa
3aa
3aa
3ca
3da
3ea
99
78
64
63
80
Trace
90
79
70
48
54
48
56
78
89
58
80
57
90
95
90
87
56[d]
-33
72
78
-32
-15
60
18
44
48
64
77
16
84
88
86
88
VI
IV
IV
IV
IV
IV
IV
IV
IV
IV
IV
IV
IV
IV
IV
IV
IV
9
9
22
24
24
24
96
72
24
48
64
96
48
36
24
12
10
11
12
13
14[e]
15[e]
16[e]
17[e]
18[e]
19[f]
20[f]
21[f]
22[f]
0
À20
À20
À20
À20
À50
À50
À50
À50
À50
DCE
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
92
92 g]
24
45
55
1e [Ph]
[a]
Unless otherwise noted, reactions were performed with 0.03 mmol of 1a–d, 0.02 mmol of 2a–d, and 0.002 mmol of catalyst
in 0.2 mL solvent.
Isolated yield.
[b]
[c]
[d]
[e]
[f]
Chiral HPLC.
At À508C, reaction was finished in 2 h but the ee was the same.
0.06 mmol of 1a, 0.02 mmol of 2a, and 0.002 mmol of IV in 0.2 mL solvent.
0.25 mmol of 1a, 0.05 mmol of 2a, and 0.005 mmol of IV in 0.5 mL solvent.
0.5 mmol scale, t=43 h, yield=99% (166.7 mg), ee=92%.
[g]
between the aromatic thiol 1e and 2a was fast but strates. Thus, substrates 2i, 2j–l, 2n and 2o and the
gave only moderate enantioselectivity (Table 1, electron-rich heteroaromatic 2p required 10 equiva-
entry 22).
lents of 1a for completion in reasonable reaction
Various (E)-4-oxo-4-arylbutenamides 2e–p contain- times (Table 2, entries 5–8 and 10–12). The reigo-
ing 2-oxazolidinone as amide moiety were examined, chemistry of the adducts was confirmed by NOE anal-
and the results are summarized in Table 2. Excellent ysis of 3ao.[12] (E)-4-Oxo-4-methylbutenamide 2q, con-
ee values (up to 97% ee) were obtained under the es- taining an aliphatic ketone moiety, was tested in the
tablished reaction conditions. The results revealed reaction with 1a (Table 2, entry 13). We found that
that the enantioselectivity of the reaction was not sen- the reaction was very slow even at higher temperature
sitive to the electronic effects of substituted groups on (À208C) with moderate enantioselectivity.
the aromatic rings. Reaction rates were determinately
Other than (E)-4-oxo-4-arylbutenamides, (E)-4-
affected by tuning the electronic effects of the sub- oxo-4-arylbutenones 4 were also used as acceptors in
2626
asc.wiley-vch.de
ꢁ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2011, 353, 2624 – 2630

Synthesis of Sulfur-Substituted a-Stereogenic Amides and Ketones
Table 2. Asymmetric addition of TBM 1a to (E)-4-oxo-4-arylbutenamides 2e–q catalyzed by IV.[a]
Entry
2 [R]
t [h]
3
Yield [%][b]
ee [%][c]
1
2
3
4
2e [p-CF3-C6H4]
2f [p-F-C6H4]
2g [p-Cl-C6H4]
2h [p-Br-C6H4]
2i [p-Ph-C6H4]
2j [m-CN-C6H4]
2k [m-Br-C6H4]
2l [m-MeO-C6H4]
2m [o-NO2-C6H4]
2n [o-F-C6H4]
2o [2-naphthyl]
2p [2-thienyl]
2q [Me]
60
56
42
29
60
60
60
48
29
60
50
90
72
3ae
3af
3ag
3ah
3ai
3aj
3ak
3al
3am
3an
3ao
3ap
3aq
80
84
97
90
84
80
92
80
75
85
91
81
45
94
92
94
97
95
90
5[d]
6[d]
7[d]
8[d]
9
94
92[e]
86
10[d]
11[d]
12[d]
13[e]
91[e]
98
92
62
[a]
Unless otherwise noted, reactions were performed with 0.25 mmol of 1a, 0.05 mmol of 2, and 0.005 mmol of catalyst in
0.5 mL solvent.
Isolated yield.
Chiral HPLC.
[b]
[c]
[d]
[e]
Reactions were performed with 0.50 mmol of 1a, 0.05 mmol of 2, and 0.005 mmol of catalyst in 0.5 mL solvent.
The reaction was conducted at À208C.
the asymmetric sulfa-Michael additions. The reaction
Table 3. Investigation of conditions for the asymmetric addi-
tion of TBM 1a to (E)-4-oxo-4-arylbutenones 4a catalyzed
by IV.[a]
between 1a and 4a with a 5:1 ratio was catalyzed by
10 mol% IV in dichloromethane at À508C (Table 3,
entry 1). After 96 h, the adduct 5aa was obtained with
98% yield and 80% ee. The reaction rate can be im-
proved by increasing the amount of 1a (Table 3, en-
tries 2 and 3). It is well known that highly concentrat-
ed reaction conditions can enhance the reaction rate
in organic synthesis. Thus, 1a which has a high melting
point (À1.18C) was tested as co-solvent with DCM to
improve the reaction rate (Table 3, entries 4–7). We
found that the reaction rate was accelerated at higher
concentrations without compromising the enantiose-
lectivity when the ratio of 1a:DCM was increased
from 1:3 to 1:1. The best ratio was found to be 2:1,
and 86% ee of 5aa in excellent yield was achieved
after 9 h at À608C (Table 3, entry 7). Under the high
concentration conditions, less than 5% of the regioiso-
Entry 1a:4a 1a:DCM T [oC] t [h] Yield [%][b] ee [%][c]
1
2
3
5:1
10:1
20:1
–
–
–
–
–
–
1:3
1:1
1:1
2:1
À50
À50
À50
À50
À50
À60
À60
96
42
42
29
9
98
56
90
80
99
99
93
80
80
81
80
82
86
86[f]
4[d]
5[d]
6[d]
7[e]
17
9
–
[a]
1
Unless otherwise noted, reactions were performed with
0.02 mmol scale in 0.2 mL dichloromethane.
Isolated yield.
mer of 5aa was detected from crude H NMR. How-
ever, the surplus of 1a and the regioisomer of 5aa
could be easily removed by flash column chromatog-
raphy.
Using the optimized conditions, (E)-4-oxo-4-aryl-
AHCTUNGTREGbNNUN utenones 4b–j (Table 4) were subjected to sulfa-Mi-
chael addition with TBM 1a. Most of reactions were
completed within 20 h. The adducts 5ab–aj were ob-
tained in high yields and good to excellent ees. The
regioisomers for some reactions were detected in
[b]
[c]
[d]
Chiral HPLC.
Reactions were performed with 0.02 mmol scale in
0.2 mL mixed solvent of BSM 1a and dichloromethane
with different ratios.
Reactions were performed with 0.05 mmol scale in
0.5 mL solvent (1a:DCM=2:1).
[e]
[f]
0.5 mmol scale, t=12 h, yield=80% (106.4 mg), ee=
86%.
Adv. Synth. Catal. 2011, 353, 2624 – 2630
ꢁ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
2627

Fangli Zhao et al.
COMMUNICATIONS
Table 4. Asymmetric addition of TBM 1a to (E)-4-oxo-4-ar-
ylbutenones 4b–j catalyzed by IV.[a]
Experimental Section
General Procedure for the Addition of tert-Butyl
Mercaptan 1a to (E)-4-Oxo-4-arylbutenamides 2a and
2e–p Catalyzed by IV
(E)-4-Oxo-4-arylbutenamides 2a, 2e–p (0.05 mmol, 1 equiv.)
and IV (2.8 mg, 0.005 mmol, 0.1 equiv.) were dissolved in di-
chloromethane (500 mL) in 4-mL sample vials and stirred at
the required temperature (À50 to À208C) for 30 min. Then
tert-butyl mercaptan 1a (0.25 mmol/28 mL or 0.50 mmol/
56 mL) was added. The reacting mixtures were stirred and
maintained at the desired temperature and the reaction
progress was monitored by TLC. Upon complete consump-
tion of the (E)-4-oxo-4-arylbutenamides 2a and 2e–p, the re-
action mixtures were loaded onto a short silica gel column,
followed by separation with flash chromatography using gra-
dient elution with PE (petroleum ether)/EA mixtures (10:1
to 2:1). After the removal of solvent under vacuum, prod-
ucts 3aa and 3ae–ap were obtained.
Entry 4 [Ar]
n
t
5
Yield
[%][b]
ee
[h]
[%][c]
1
2
3
4
5
6
7
4b [p-CF3-C6H4]
0
0
0
0
0
0
0
15
6
6
5ab 78
5ac 87
5ad 91
5ae 80
5af
5ag 87
5ah 90
87
90
86
86
90
90
90
4c [p-F-C6H4]
4d [p-Cl-C6H4]
4e [p-Br-C6H4]
4f [p-MeO-C6H4]
4g [m-NO2-C6H4]
4h [m-MeO-
C6H4]
6
33
20
6
86
8
9
4i [2-thienyl]
4j [m-MeO-
C6H4]
0
2
30
15
5ai
5aj
91
75
88
87
General Procedure for the Addition of tert-Butyl
Mercaptan 1a to (E)-4-Oxo-4-arylbutenones 4a–j
Catalyzed by IV
[a]
Unless otherwise noted, reactions were performed with
0.05 mmol scale in 0.5 mL solvent (1a:DCM=2:1).
Isolated yield.
[b]
[c]
Catalyst IV (2.8 mg, 0.005 mmol, 0.1 equiv.) and tert-butyl
mercaptan 1a (333 mL) were dissolved in dichloromethane
(167 mL) in 4-mL sample vials. After stirring at À608C for
Chiral HPLC.
30 min,
(E)-4-oxo-4-arylbutenones
4a–j
(0.05 mmol,
small amount (less than 10%). The absolute configu-
rations of the sulfa-Michael addition products were
assigned as S based on an X-ray crystallographic anal-
ysis of single crystal 5ad.[13] Furthermore, we demon-
strated that the a-stereogenic ester 6 could be
smoothly achieved from the corresponding a-stereo-
genic amide 3ag without compromising the ee value
[Eq. (3)].[7j]
1 equiv.) was added. The reaction mixtures were stirred at
À608C and monitored by TLC. Upon complete consump-
tion of the (E)-4-oxo-4-arylbutenones 4a–j, the reaction
mixtures were loaded onto a short silica gel column, fol-
lowed by flash chromatography using gradient elution with
PE (petroleum ether)/EA mixtures (20:1 to 10:1). Remov-
ing the solvent under vacuum, afforded products 5aa and
5ae–aj.
In summary, we have developed a highly enantiose-
lective and regioselective organocatalytic sulfa-Mi-
chael addition of tert-butyl mercaptan to (E)-4-oxo-4-
Supporting Information
Experimental procedures, characterization and spectroscopic
data (PDF) are available in the Supporting Information.
arylbutenamides
and
(E)-4-oxo-4-arylbutenones,
which provides a new avenue to the construction of
the chiral sulfur-containing centers a to the amide
and ketone groups. To the best of our knowledge, this
is the first example of the organocatalyzed enantiose-
lective synthesis of sulfur-substituted a-stereogenic
amides and ketones. Further studies on the synthesis
of other useful chiral a-stereogenic amides and ke-
tones using different donors are undergoing in our
laboratories.
Acknowledgements
We are grateful for the financial support from NSFC
(21072044) (Z.J.), Excellent Youth Foundation of Henan Sci-
entific Committee (114100510003) (Z.J.), International Coop-
eration Foundation of Henan Province (104300510062) (Z.J.
and C.-H.T.), and ARF (R-143-000-337-112) (C.-H.T).
2628
asc.wiley-vch.de
ꢁ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2011, 353, 2624 – 2630

Synthesis of Sulfur-Substituted a-Stereogenic Amides and Ketones
References
Lu, F.-G. Zhang, X.-G. Meng, S.-W. Duan, W.-J. Xiao,
Org. Lett. 2009, 11, 3946–3949; n) S. Lin, D. Leow, K.-
W. Huang, C.-H. Tan, Chem. Asian J. 2009, 4, 1741–
1744; o) P. Ricci, A. Carlone, G. Bartoli, M. Bosco, L.
Sambri, P. Melchiorre, Adv. Synth. Catal. 2008, 350, 49–
53; p) D. Leow, S. Lin, S. K. Chittimalla, X. Fu, C.-H.
Tan, Angew. Chem. 2008, 120, 5723–5727; Angew.
Chem. Int. Ed. 2008, 47, 5641–5645; q) P. McDaid, Y.
Chen, L. Deng, Angew. Chem. 2002, 114, 348–350;
Angew. Chem. Int. Ed. 2002, 41, 338–340; r) A. Kumar,
R. V. Salunkhe, R. A. Rane, S. Y. Dike, J. Chem. Soc.
Chem. Commun. 1991, 485–486; for selected examples
of cascade organocatalytic asymmetric sulfa-Michael
addition, see: s) P. Galzerano, F. Pesciaioli, A. Mazzan-
ti, G. Bartoli, P. Melchiorre, Angew. Chem. 2009, 121,
8032–8034; Angew. Chem. Int. Ed. 2009, 48, 7892–7894;
t) J. Wang, H. Xie, H. Li, L. Zu, W. Wang, Angew.
Chem. 2008, 120, 4245–4247; Angew. Chem. Int. Ed.
2008, 47, 4177–4179; u) L. Zu, J. Wang, H. Li, H. Xie,
W. Jiang, W. Wang, J. Am. Chem. Soc. 2007, 129, 1036–
1037; v) S. Brandau, E. Maerten, K. A. Jørgensen, J.
Am. Chem. Soc. 2006, 128, 14986–14991; w) R. Rios, H.
SundØn, I. Ibrahem, G.-L. Zhao, A. Córdova, Tetrahe-
dron Lett. 2006, 47, 8679–8682.
[1] J. J. R. Frafflsto da Silva, R. J. P. Williams, The Biologi-
cal Chemistry of the Elements, Oxford University Press,
New Work, 2001.
[2] a) M.-J. Jin, S. M. Sarkar, D.-H. Lee, H. Qiu, Org. Lett.
2008, 10, 1235–1237; b) H.-L. Wu, P.-Y. Wu, B.-J. Uang,
J. Org. Chem. 2007, 72, 5935–5937; c) P.-Y. Wu, H.-L.
Wu, B.-J. Uang, J. Org. Chem. 2006, 71, 833–835;
d) A. M. Arink, T. W. Braam, R. Keeris, J. T. B. H.
Jastrzebski, C. Benhaim, S. Rosset, A. Alexakis, G. V.
van Koten, Org. Lett. 2004, 6, 1959–1962; e) D. A.
Evans, F. E. Michael, J. S. Tedrow, K. R. Campos, J.
Am. Chem. Soc. 2003, 125, 3534–3543; f) D. A. Evans,
K. R. Campos, J. S. Tedrow, F. E. Michael, M. R.
GagnØ, J. Am. Chem. Soc. 2000, 122, 7905–7920;
g) J. C. Anderson, M. Harding, Chem. Commun. 1998,
393–394.
[3] a) E. M. McGarrigle, V. K. Aggarwal, in: Enantioselec-
tive Organocatalysis, (Ed.: P. Dalko), Wiley-VCH,
Weinheim, Germany, 2007, Chap. 10, p 357; b) E. M.
McGarrigle, E. L. Myer, O. Illa, M. A. Shaw, S. L.
Riches, V. K. Aggarwal, Chem. Rev. 2007, 107, 5841–
5883; c) C. E. Aroyan, S. J. Miller, J. Am. Chem. Soc.
2007, 129, 256–257.
[4] a) J.-F. Bri›re, P. Metzner, in: Organosulfur Chemistry
in Asymmetric Synthesis, (Eds.: T. Toru, C. Bolm),
Wiely-VCH, Weinheim, Germany, 2008, Chap. 5, p 179;
b) G. Y. Fang, O. A. Wallner, N. Di Blasio, X. Ginesta,
J. N. Harvey, V. K. Aggarwal, J. Am. Chem. Soc. 2007,
129, 14632–14639; c) S. Fanjul, A. N. Hulme, J. W.
White, Org. Lett. 2006, 8, 4219–4222; d) M. T. Crim-
mins, B. W. King, E. A. Tabet, K. Chaudhary, J. Org.
Chem. 2001, 66, 894–902; e) B. H. Kim, D. P. Curran,
Tetrahedron 1993, 49, 293–318.
[5] a) Organosulfur Chemistry in Asymmetric Synthesis,
(Eds.: T. Toru, C. Bolm), Wiely-VCH, Weinheim, Ger-
many, 2008; b) D. Enders, K. Lüttgen, A. A. Narine,
Synthesis 2007, 959–980.
[7] D. Seebach, Angew. Chem. 1979, 91, 259–278; Angew.
Chem. Int. Ed. Engl. 1979, 18, 239–258.
[8] For a selected review, see: a) M. Whittaker, C. D.
Floyd, P. Brown, A. J. H. Gearing, Chem. Rev. 1999, 99,
2735–2776; for the selected example, see: b) S.-J. Wen,
Z.-J. Yao, Org. Lett. 2004, 6, 2721–2724.
[9] For examples on the synthesis of a-stereogenic amides
and ketones, see: a) Z. Jiang, Y. Yang, Y. Pan, Y. Zhao,
H. Liu, C.-H. Tan, Chem. Eur. J. 2009, 15, 4925–4930;
b) J. L. Zigterman, J. C. S. Woo, S. D. Walker, J. S.
Tedrow, C. J. Borths, E. E. Bunel, M. M. Faul, J. Org.
Chem. 2007, 72, 8870–8876; c) M. P. Sibi, S. Manyem,
H. Palencia, J. Am. Chem. Soc. 2006, 128, 13660–13661;
d) S. D. Bull, S. G. Davies, A. C. Garner, D. Kruchinin,
M.-S. Key, P. M. Roberts, E. D. Savory, A. D. Smith,
J. E. Thomson, Org. Biomol. Chem. 2006, 4, 2945–2964;
e) M. P. Sibi, L. M. Stanley, C. P. Jasperse, J. Am.
Chem. Soc. 2005, 127, 8276–8277; f) C. Fischer, G. C.
Fu, J. Am. Chem. Soc. 2005, 127, 4594–4595; g) R.
Shintani, K. Ueyama, I. Yamada, T. Hayashi, Org. Lett.
[6] For selected examples of organometallic-catalyzed
asymmetric sulfa-Michael addition, see: a) M. Ueno, T.
Kitanosono, M. Sakai, S. Kobayashi, Org. Biomol.
Chem. 2011, 9, 3619–3621; b) Y. Hui, J. Jiang, W. Wang,
W. Chen, Y. Cai, L. Lin, X. Liu, X. Feng, Angew.
˘
ˇ
ˇ
Chem. Int. Ed. 2010, 49, 4290–4293; c) A. Badoiu, G.
2004, 6, 3425–3427; h) P. Jakubec, D. Berkes, F. Povaza-
nec, Tetrahedron Lett. 2004, 45, 4755–4758; i) H. Kakei,
T. Nemoto, T. Ohshima, M. Shibasaki, Angew. Chem.
2004, 116, 321–324; Angew. Chem. Int. Ed. 2004, 43,
317–320; j) G. Li, X. Xu, D. Chen, C. Timmons, M. D.
Carducci, A. D. Headley, Org. Lett. 2003, 5, 329–331;
k) D. A. Evan, S. J. Miller, T. Lectka, P. V. Matt, J. Am.
Chem. Soc. 1999, 121, 7559–7573; l) N. A. Porter, D. M.
Scott, I. J. Rosenstein, B. Giese, A. Veit, H. G. Zeitz, J.
Am. Chem. Soc. 1991, 113, 1791–1799.
Bernardinelli, C. Besnard, E. P. Kündig, Org. Biomol.
Chem. 2010, 8, 193–200; d) M. Kawatsura, Y. Komatsu,
M. Yamamoto, S. Hayase, T. Itoh, Tetrahedron 2008,
64, 3488–3493; e) A. M. M. Abe, S. J. K. Sauerland,
A. M. P. Koskinen, J. Org. Chem. 2007, 72, 5411–5413;
f) M. Saito, M. Nakajima, S. Hashimoto, Chem.
Commun. 2000, 1851–1852; for selected examples of
direct organocatalytic asymmetric sulfa-Michael addi-
tion, see: g) M. Yoshida, Y. Ohno, S. Hara, Tetrahedron
Lett. 2010, 51, 5134–5136; h) L. Dai, S.-X. Wang, F.-E.
Chen, Adv. Synth. Catal. 2010, 352, 2137–2141; i) J. Sun,
G. C. Fu, J. Am. Chem. Soc. 2010, 132, 4568–4569;
j) N. K. Rana, S. Selvakumar, V. K. Singh, J. Org.
Chem. 2010, 75, 2089–2091; k) K. L. Kimmel, M. T.
Robak, J. A. Ellman, J. Am. Chem. Soc. 2009, 131,
8754–8755; l) Y. Liu, B. Sun, B. Wang, M. Wakem, L.
Deng, J. Am. Chem. Soc. 2009, 131, 418–419; m) H.-H.
[10] a) Y. Zhao, Y. Pan, H. Liu, Y. Yang, Z. Jiang, C.-H.
Tan, Chem. Eur. J. 2011, 17, 3571–3574; b) J. Wang, H.
Liu, Y. Fan, Y. Yang, Z. Jiang, C.-H. Tan, Chem. Eur. J.
2010, 16, 12534–12537; c) Y. Pan, Y. Zhao, T. Ma, Y.
Yang, H. Liu, Z. Jiang, C.-H. Tan, Chem. Eur. J. 2010,
16, 779–782; d) Z. Jiang, Y. Pan, Y. Zhao, T. Ma, R.
Lee, Y. Yang, K.-W. Huang, M. W. Wong, C.-H. Tan,
Angew. Chem. 2009, 121, 3681–3685; Angew. Chem.
Adv. Synth. Catal. 2011, 353, 2624 – 2630
ꢁ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
2629

Fangli Zhao et al.
COMMUNICATIONS
Int. Ed. 2009, 48, 3627–3631; e) H. Liu, D. Leow, K.-W.
Huang, C.-H. Tan, J. Am. Chem. Soc. 2009, 131, 7212–
7213; f) Z. Jiang, W. Ye, Y. Yang, Adv. Synth. Catal.
2008, 350, 2345–2351; g) W. Ye, Z. Jiang, Y. Zhao,
Serena L. M. Goh, D. Leow, Y.-T. Soh, C.-H. Tan, Adv.
Synth. Catal. 2007, 349, 2454–2458; h) X. Fu, Z. Jiang,
C.-H. Tan, Chem. Commun. 2007, 5058–5060; i) J. Shen,
T. T. Nguyen, Y.-P. Goh, W. Ye, X. Fu, J. Xu, C.-H.
Tan, J. Am. Chem. Soc. 2006, 128, 13692–13693.
sen, Chem. Rev. 2007, 107, 5713–5743; d) M. S. Taylor,
E. N. Jacobsen, Angew. Chem. 2006, 118, 1550–1573;
Angew. Chem. Int. Ed. 2006, 45, 1520–1543; e) T.
Akiyama, J. Itoh, K. Fuchibe, Adv. Synth. Catal. 2006,
348, 999–1010; f) P. R. Schreiner, Chem. Soc. Rev. 2003,
32, 289–296.
[12] See the Supporting Information for details.
[13] CCDC 817603 (5ad) contains the supplementary crys-
tallographic data for this paper. These data can be ob-
tained free of charge from The Cambridge Crystallo-
graphic Data Centre via www.ccdc.cam.ac.uk/data_re-
quest/cif.
[11] For selected reviews, see: a) S. J. Connon, Chem.
Commun. 2008, 2499–2510; b) X. Yu, W. Wang, Chem.
Asian J. 2008, 3, 516–532; c) A. G. Doyle, E. N. Jacob-
2630
asc.wiley-vch.de
ꢁ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2011, 353, 2624 – 2630