(S)-Pyrrolidine sulfonamide catalyzed asymmetric direct aldol reactions of aryl methyl ketones with aryl aldehydes

Article abstract of DOI:10.1016/j.tetlet.2008.02.164

A (S)-pyrrolidine sulfonamide catalyzed asymmetric direct aldol reaction of aryl methyl ketones with aromatic aldehydes has been developed with moderate to good enantioselectivities. The study considerably broadens the substrate scope of chiral amines pro

Full text of DOI:10.1016/j.tetlet.2008.02.164

Available online at www.sciencedirect.com
Tetrahedron Letters 49 (2008) 2681–2684
(S)-Pyrrolidine sulfonamide catalyzed asymmetric direct
aldol reactions of aryl methyl ketones with aryl aldehydes
a
a,
b
a
a
a
a
*
Kui Mei , Shilei Zhang , Songtao He , Ping Li , Mei Jin , Fei Xue , Guangshun Luo ,
Haoyi Zhang a, Lirong Song a, Wenhu Duan a,b,*, Wei Wang a,c,
*
a Department of Pharmaceutical Sciences, School of Pharmacy, East China University of Science and Technology, Shanghai 200237,
People’s Republic of China
b Shanghai Institute of Materia Medica, Shanghai Institutes of Biological Sciences, Chinese Academy of Sciences,
Graduate School of the Chinese Academy of Sciences, Shanghai 201203, People’s Republic of China
c Department of Chemistry and Chemical Biology, University of New Mexico, Albuqueruqe, NM 87131-0001, USA
Received 9 January 2008; revised 17 February 2008; accepted 29 February 2008
Available online 5 March 2008
Abstract
A (S)-pyrrolidine sulfonamide catalyzed asymmetric direct aldol reaction of aryl methyl ketones with aromatic aldehydes has been
developed with moderate to good enantioselectivities. The study considerably broadens the substrate scope of chiral amines promoted
aldol processes.
Ó 2008 Elsevier Ltd. All rights reserved.
Keywords: Aldol reaction; Aryl alkyl ketones; Pyrrolidine sulfonamide
The seminal work by List et al. using L-proline catalyzed
direct intermolecular aldol reactions has triggered a broad
interest in organocatalysis.1 Subsequently, a number of
research groups have developed proline analogues for the
aldol process aimed at improving reactivity, broadening
substrate scope and enhancing stereoselectivity.2,3 Despite
the fact that in many cases, these proline analogues
displayed high catalytic activity and enantio- and diastereo-
selectivity, they suffered from a narrow substrate scope.
For example, it was found that when ketones were used
as donors, they were restricted to ones with alkyl groups
at both ends. In contrast, the use of less reactive aryl alkyl
ketones has created a formidable challenge and the survey
of the literature reveals that only single study was reported
by Saito and Yamamoto.3g The process was catalyzed by
proline-derived tetrazole in low to high yields (35–93%)
and with moderate to high ees (67–97%), but only worked
out for highly active trichloro- and trifluoroacetaldehydes
as aldol acceptor. Therefore, the general methods mainly
rely on the indirect chiral Lewis acid catalyzed asymmetric
Mukaiyama aldol reaction of preformed silyl enol ethers.4
As a result of this deficiency, we have recently initiated
an investigation aimed at broadening the scope of chiral
amines catalyzed direct cross aldol reactions. In this Letter,
we report the results of a study which has led to the devel-
opment of a (S)-pyrrolidine sulfonamide promoted a direct
aldol reaction of aromatic methyl ketones with aromatic
aldehydes in high efficiency.5,6
To identify active promoters for the activation of less
reactive aryl methyl ketones, our investigation began with
the design of new bifunctional amines and screening of
them including some known organocatalysts (Fig. 1). Our
strategy in the design of more active bifunctional amine
catalysts is the incorporation of acidic groups, which can
effectively activate aldol acceptors. In the recent past, thio-
ureas with the ability of affording two H-bond donors have
been widely used as general acid for effective activation of
*
Corresponding authors. Tel.: +86 21 6425 1973 (S.Z.); tel.: +86 21
5080 6032 (W.D.); tel.: +1 505 277 0756; fax: +1 505 277 2609 (W.W.).
E-mail addresses: zhangshilei@ecust.edu.cn (S. Zhang), wduan@
mail.shcnc.ac.cn (W. Duan), wwang@unm.edu (W. Wang).
0040-4039/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2008.02.164

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K. Mei et al. / Tetrahedron Letters 49 (2008) 2681–2684
Table 1
H
H
H
S
N
N
H
H
Asymmetric direct aldol reaction of phenyl methyl ketone with p-
nitrobenzaldehyde catalyzed by organocatalysts 1a–ja
O
Ar
S
N
S
S
N
N
S
Ar
S
CF3
O
NH2
S
NH
S
S
O
OH
NH2
Tf
OHC
+
O
O
cat. (10 mol %)
R
Ph
1c
1a: Ar = Ph
1b: Ar = 3, 5-(CF3)2C6H3
HN
Ph
CHCl3, rt
NO2
NO2
4a
1d: Ar = Ph
2a
3a
1e: Ar = 3, 5-(CF3)2C6H3
Entry
Cat
t (d)
Yieldb (%)
eec (%)
1
2
3
4
5
6
7
8
1a
1b
1c
1d
1e
1f
5
5
5
5
5
5
5
3
5
5
19
16
7
14
8
6
5
S
S
NHTf
NH
S
S
NHTf
NH
NHTf
N
H
H
N
H
ꢀ7
ꢀ12
ꢀ11
ꢀ7
16
21
15
—
1h
N
Ph
N
H
O
S
O
S
R
1i
CO2H
N
H
10
11
76
20
HN
HN
1f
1j
1g
1g
1h
1i
Fig. 1. Organocatalysts evaluated in the direct cross aldol reaction.
9
10
a
d
1j
—
carbonyl groups with a great success.7 Furthermore, we
have found that acidic sulfonamides are also strong activa-
tors for electrophiles.5 On the other hand, recently, chiral
primary amines have gained a great deal of interest in
organocatalysis.8 They have been shown to serve as effec-
tive activators for facilitating the forming enamines from
ketones and aldehydes. In particular, Jacobsen and
co-workers have demonstrated that primary amine thio-
ureas can efficiently catalyze aromatic alkyl ketones to
produce enamines for a highly enantioselective conjugate
nitroalkene addition process.8d With these considerations
in mind, we designed and synthesized chiral bifunctional
trans-cyclohexanediamine-based organic catalysts 1a–g,
which consist of these functional groups.9
The reaction was carried out with 3a (0.2 mmol) and 2a (1.0 mmol,
5 equiv) in the presence of 10 mol % an organocatalyst in 0.3 mL of CHCl3
at rt.
b
Isolated yield.
c
Determined by chiral HPLC analysis (Chirapak AD-H column).
No desired product was obtained.
d
Table 2
Effects of solvents and additives on the asymmetric direct aldol reaction of
phenyl methyl ketone and p-nitrobenzaldehyde catalyzed by 1ha
O
OH
OHC
+
O
1h (10 mol %)
Ph
Ph
additive (0.1 eq)
solvent, 3d
NO2
NO2
4a
2a
3a
Solvent
Entry
Additive
Yieldb (%)
eec (%)
To explore their catalytic ability of these organocata-
lysts for aldol process, a model reaction between phenyl
methyl ketone 2a and p-nitrobenzaldehyde 3a was per-
formed in chloroform at room temperature in the presence
of 10 mol % an organocatalyst (Table 1). As revealed in
Table 1, their catalytic activities varied significantly.
Disappointingly, these new organocatalysts 1a–g exhibited
poor catalyst activity for the aldol reaction (entries 1–7).
Poor reaction yields (8–19%) and low enantioselectivities
(5–16% ee) were obtained with long reaction times (5 d).
A similar trend was observed for catalyst (S)-pyrrolidine
thiourea 1i (entry 9). No desired product was formed when
(S)-proline was used and only a by-product bicyclic 1,3-
oxazolidine10 resulted from the reaction of the catalyst with
p-nitrobenzaldehyde isolated in 58% yield based on (S)-
proline (entry 10). Among the organocatalysts probed, it
was found that (S)-pyrrolidine sulfonamide 1h5 displayed
high catalytic activity for the aldol reaction in a good yield
(76%), but the enantioselectivity was low (21% ee, Table 1,
entry 8). Subsequently, catalyst 1h was selected for further
condition optimizations mainly aimed at improving enantio-
selectivity of the aldol process.
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16d
a
CHCl3
Toluene
Dioxane
THF
MeCN
i-PrOH
H2O
None
None
None
None
None
None
None
None
76
30
46
38
72
46
67
71
74
37
41
<5
81
86
72
45
21
25
30
47
51
11
50
70
82
81
82
nde
82
82
81
90
DMF
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
None
AcOH
PhCO2H
CF3CO2H
H2O (0.5 equiv)
H2O (1.0 equiv)
H2O (5.0 equiv)
H2O (1.0 equiv)
Unless stated otherwise, the reaction was carried out with 1.0 mmol
(0.12 mL, 5 equiv) 2a and 0.2 mmol 3a in the presence of 10 mol % catalyst
in 0.3 mL of solvent and stirred at rt for 3 d.
b
Isolated yield.
Determined by chiral HPLC analysis.
0 °C, 2.0 mmol (0.24 mL, 10 equiv) 2a was used, 5 d.
Not determined.
c
d
e
We first investigated the solvent effect on the cross aldol
reaction. As shown in Table 2, the reaction yields and
enantioselectivities were highly solvent dependent. Lower
enantioselectivity was observed when less polar aprotic
solvents were used (entries 1–5), while more polar ones
afforded aldol adduct 4a with significant improved ees
(entries 8 and 9). Notably, a high level of enantioselectivity
(82% ee, entry 9) was achieved with DMSO (analytic

K. Mei et al. / Tetrahedron Letters 49 (2008) 2681–2684
2683
grade). Protic solvents such as i-PrOH and water tested
seemed to have an adverse influence on enantioselectivity
(entries 6 and 7). A possible reason for the aprotic polar
solvent DMSO afford the best results was due to its ability
of stabilizing the charged transition state, while protic sol-
vents disrupted the transition state. The effect of additives
in DMSO on enantioselectivity was also probed. Acid
additives such as AcOH, PhCO2H and CF3CO2H retarded
the process and the reaction yields dropped dramatically
but without affecting ee values (entries 10–12); it was found
that water could increase the yield slightly, but it did not
deteriorate the enantioselectivity either (Table 2, entry
13–15). Scrutinizing the amount of water implied that the
use of 1.0 equiv was optimal in terms of reaction yield
and enantioselectivity (entry 14). Finally, lowering the tem-
perature to 0 °C increased the ee of the product from 82%
to 90% but the yield decreased significantly from 86% to
45% (Table 2, entry 14 vs entry 16).
Having established optimized conditions for the model
reaction, we next probed the generality of this asymmetric
direct aldol reaction with a wide range of aromatic ketones
and aryl aldehydes (Table 3). Aromatic methyl ketones
bearing various substituents were first investigated as aldol
donors with p-nitrobenzaldehyde (Table 3, entries 1–7).
The neutral (entry 1), electron-withdrawing (entries 2–4),
-donating (entries 5–6), and heterocyclic (entry 7) groups
could be tolerated in the 1h-promoted aldol processes.
Moderate to good yields (47–91%) and moderate to high
ees (62–87%) were observed. The study in a variation of
aldol donors revealed that the reaction yields varied signif-
icantly, but the enantioselectivity was not affected much
with achieving moderate to high levels of enantioselectivity
(71–87% ee, entries 8–17). Low reaction yields were
attained when phenyl methyl ketone was used as aldol
donor (entries 8–13). Similar observation was noticed with
p-MeO-benzaldehyde (entries 16–17). However, p-NO2-
benzaldehyde afforded aldol adducts with higher yields
(83–87%, entries 14 and 15).
The absolute configuration of aldol products was deter-
mined to be R by comparison of the optical rotation value
and sign of 4m with those of the literature reported.11
In conclusion, we have developed a (S) pyrrolidine sulf-
onamide 1h catalyzed asymmetric aldol reaction of aro-
matic methyl ketones with aromatic aldehydes. Moderate
to good enantioselectivities were obtained under the opti-
mized reaction conditions. The study considerably widens
the substrate scope of chiral amine promoted direct aldol
processes by allowing the use of difficult aromatic methyl
ketones for aldol reaction with aromatic aldehydes. A full
scope of investigation of the strategy is underway in our
laboratory.
Acknowledgments
This work was supported by Shanghai Basic Research
Project from the Shanghai Science and Technology Com-
mission (Grants 06JC14080) and start-up funding from
School of Pharmacy, East China University of Science
and Technology.
Table 3
Scope of catalyst 1h catalyzed asymmetric aldol reactions of aryl methyl
ketones with aryl aldehydesa
10 mol % 1h
H2O (1.0 eq)
O
O
O
OH
Ar2
Supplementary data
+
H
Ar2
Ar1
Ar1
DMSO, rt
2
3
4
Supplementary data associated with this article can be
found, in the online version, at doi:10.1016/j.tetlet.2008.
02.164.
Entry
Ar1
Ph
Ar2
t (d)
Yieldb (%)
eec (%)
1
2
3
4
5
6
7
8
9
p-NO2C6H4
p-NO2C6H4
p-NO2C6H4
p-NO2C6H4
p-NO2C6H4
p-NO2C6H4
p-NO2C6H4
o-NO2C6H4
m-NO2C6H4
p-FC6H4
3
2
3
3
3
3
5
3
3
5
5
5
5
2
2
4
3
4a, 74
4b, 91
4c, 74
4d, 47
4e, 65
4f, 77
4g, 51
4h, 68
4i, 45
4j, 32
4k, 26
4l, 31
4m, 18
4n, 87
4o, 83
4p, 51
4q, 57
82
70
76
80
79
87
62
87
81
73
80
76
80
71
80
80
91
p-NO2C6H4
p-ClC6H4
2,4-Cl2C6H3
p-MeOC6H4
p-MeC6H4
o-Thienyl
Ph
Ph
Ph
Ph
Ph
References and notes
1. List, B.; Lerner, R. A.; Barbas, C. F., III. J. Am. Chem. Soc. 2000,
122, 2395.
2. Recent reviews of chiral secondary amine catalyzed enamine chem-
istry, see: (a) List, B. Acc. Chem. Res. 2004, 37, 548; (b) Notz, W.;
Tanaka, F.; Barbas, C. F., III. Acc. Chem. Res. 2004, 37, 580; (c)
Mukherjee, S.; Yang, J. W.; Hoffmann, S.; List, B. Chem. Rev. 2007,
107, 5471.
3. Selected examples of proline analogues catalyzed aldol reactions, see:
(a) Sakthivel, K.; Notz, W.; Bui, T.; Barbas, C. F., III. J. Am. Chem.
Soc. 2001, 123, 5260; (b) Saito, S.; Nakadai, M.; Yamamoto, H.
Synlett 2001, 1245; (c) Tang, Z.; Jiang, F.; Yu, L.-T.; Cui, X.; Gong,
L.-Z.; Mi, A.-Q.; Jiang, Y.-Z.; Wu, Y.-D. J. Am. Chem. Soc. 2003,
125, 5262; (d) Krattiger, P.; McCarthy, C.; Pfaltz, A.; Wennemers, H.
Angew. Chem., Int. Ed. 2003, 42, 1722; (e) Kofoed, J.; Nielsen, J.;
Reymond, J.-L. Bioorg. Med. Chem. Lett. 2003, 13, 2445; (f) Cobb, A.
J. A.; Shaw, D. M.; Ley, S. V. Synlett 2004, 558; (g) Torii, H.;
Nakadai, M.; Ishihara, K.; Saito, S.; Yamamoto, H. Angew. Chem.,
Int. Ed. 2004, 43, 1983; (h) Lacoste, E.; Landais, Y.; Schenk, K.;
Verlhac, J.-B.; Vincent, J.-M. Tetrahedron Lett. 2004, 45, 8035; (i)
10
11
12
13
14
15
16
17
a
p-BrC6H4
o-BrC6H4
Ph
Ph
p-NO2C6H4
p-NO2C6H4
p-MeOC6H4
p-MeOC6H4
m-NO2C6H4
o-NO2C6H4
m-NO2C6H4
o-NO2C6H4
Unless stated otherwise, the reaction was carried out with 0.2 mmol 3
and 1.0 mmol (5 equiv) 2 in the presence of 10 mol % organocatalyst 1h
and water (1 equiv) in 0.3 mL of DMSO at rt.
b
Isolated yield after chromatographic purification.
Determined by chiral HPLC analysis (Chirapak AD, AS or OD-H
c
column).

2684
K. Mei et al. / Tetrahedron Letters 49 (2008) 2681–2684
Berkessel, A.; Koch, B.; Lex, J. Adv. Synth. Catal. 2004, 346, 1141; (j)
L.-S.; Wang, J.; Li, H.; Yu, X-H.; Wang, W. Org. Lett. 2006, 8, 3077;
(j) Cao, C.-L.; Sun, X.-L.; Zhou, J.-L.; Tang, Y. J. Org. Chem. 2007,
72, 4073; (k) Cao, C.-L.; Sun, X.-L.; Kang, Y.-B.; Tang, Y. Org. Lett.
2007, 9, 4151.
Mangion, I. K.; Northrup, A. B.; MacMillan, D. W. C. Angew.
Chem., Int. Ed. 2004, 43, 6722; (k) Shi, L.-X.; Sun, Q.; Ge, Z.-M.;
Zhu, Y.-Q.; Cheng, T.-M.; Li, R.-T. Synlett 2004, 2215; (l) Cobb, A.
J. A.; Shaw, D. M.; Longbottom, D. A.; Ley, S. V. Org. Biomol.
Chem. 2005, 3, 84; (m) Chimni, S. S.; Mahajan, D.; Babu, V. V. S.
Tetrahedron Lett. 2005, 46, 5617; (n) Bellis, E.; Kokotos, G.
Tetrahedron 2005, 61, 8669; (o) Chen, J.-R.; Lu, H.-H.; Li, X.-Y.;
Cheng, L.; Wan, J.; Xiao, W.-J. Org. Lett. 2005, 7, 4543; (p) Samanta,
S.; Liu, J.; Dodda, R.; Zhao, C.-G. Org. Lett. 2005, 7, 5321; (q)
Gryko, D.; Lipinski, R. Adv. Synth. Catal. 2005, 347, 1948; (r) Jiang,
M.; Zhu, S.-F.; Yang, Y.; Gong, L.-Z.; Zhou, X.-G.; Zhou, Q.-L.
Tetrahedron: Asymmetry 2006, 17, 384; (s) Silva, F.; Sawicki, M.;
Gouverneur, V. Org. Lett. 2006, 8, 5417; (t) Guillena, G.; Hita, M. C.;
Njera, C. Tetrahedron: Asymmetry 2006, 17, 729; (u) Raj, M.;
Vishnumaya, S. K.; Ginotra, S. K.; Singh, V. K. Org. Lett. 2006, 8,
4097; (v) Gryko, D.; Kowlaczyk, B.; Zawadzki, L. Synlett 2006, 1059;
(w) Cheng, C.; Sun, J.; Wang, C.; Zhang, Y.; Wei, S.; Jiang, F.; Wu,
Y. Chem. Commun. 2006, 215; (x) Gu, L.; Yu, M.; Wu, X.; Zhang, Y.;
Zhao, G. Adv. Synth. Catal. 2006, 348, 2223; (y) Mase, N.; Nakai, Y.;
Ohara, N.; Yoda, H.; Takabe, K.; Tanaka, F.; Barbas, C. F., III. J.
Am. Chem. Soc. 2006, 128, 734; (z) Hayashi, Y.; Sumiya, T.;
Takahashi, J.; Gotoh, H.; Urushima, T.; Shoji, M. Angew. Chem.,
Int. Ed. 2006, 45, 958; Kano, T.; Yamaguchi, Y.; Tanaka, Y.;
Maruoka, K. Angew. Chem., Int. Ed. 2007, 46, 1738.
6. The aromatic b-hydroxyketones are versatile building blocks in
organic synthesis and drug discovery. They can be conveniently
converted into diols and amine alcohols: as chiral ligands in catalysis:
(a) Dubrovina, N. V.; Tararov, I.; Monsees, A.; Spannenberg, A.;
Kostas, I. D.; Boerner, A. Tetrahedron: Asymmetry 2005, 16, 3640; (b)
Ohtsuka, Y.; Kubota, T.; Ikeno, T.; Nagata, T.; Yamada, T. Synlett
2000, 535; (c) Roos, G. H. P.; Donovan, A. R. Tetrahedron:
Asymmetry 1999, 10, 991; Synthesis of isoxazolines: (d) Jaeger, V.;
Buss, V.; Schwab, W. Tetrahedron Lett. 1978, 19, 3133; (e) As
intermediates for preparation of nucleoside derivatives as antiviral,
antitumor, and antidiabetic prodrug agents: Reddy, R. K.; Erion, M.
D. Patent WO 2006033709.
7. Reviews regarding thioureas catalysis: see: (a) Schreiner, P. R. Chem.
Soc. Rev. 2003, 32, 289; (b) Takemoto, Y. Org. Biomol. Chem. 2005, 3,
4299; (c) Akiyama, T.; Itoh, J.; Fuchibe, K. Adv. Synth. Catal. 2006,
348, 999; (d) Taylor, M. S.; Jacobsen, E. N. Angew. Chem., Int. Ed.
2006, 45, 1520; (e) Connon, S. J. Chem. Eur. J. 2006, 12, 5419; (f)
Doyle, A. G.; Jacobsen, E. N. Chem. Rev. 2007, 107, 5713.
8. Selected examples of chiral primary amines catalyzed reactions, see:
(a) Davies, S. G.; Sheppard, R. L.; Smith, A. D.; Thomson, J. E.
Chem. Commun. 2005, 3802; (b) Tsogoeva, S. B.; Wei, S. Tetrahedron:
Asymmetry 2005, 16, 1947; (c) Dziedzic, P.; Zou, W.; Hfren, J.;
4. For recent review of Mukaiyama-aldol reactions, see: (a) Shiina, I. In
Modern Aldol Reactions; Mahrwald, R., Ed.; Wiley-VCH: Weinheim,
2004; Vol. 2, pp 105–166; Selected examples, see: (b) Shibasaki, M.
Tetrahedron: Asymmetry 1995, 6, 71; (c) Li, H.-J.; Tian, H.-Y.; Chen,
Y.-J.; Wang, D.; Li, C.-J. Chem. Commun. 2002, 2994; (d) Mlynarski,
J.; Jankowska, J. Adv. Synth. Catal. 2005, 347, 521; (e) Li, H.-J.; Tian,
H.-Y.; Wu, Y.-C.; Chen, Y.-J.; Liu, L.; Wang, D.; Li, C.-J. Adv.
Synth. Catal. 2005, 347, 1247; (f) Itsuno, S.; Arima, S.; Haraguchi, N.
Tetrahedron 2005, 61, 12074; (g) Jankowska, J.; Paradowska, J.;
Mlynarski, J. Tetrahedron Lett. 2006, 47, 5281; (h) Jankowska, J.;
Paradowska, J.; Rakiel, B.; Mlynarski, J. J. Org. Chem. 2007, 72,
2228.
5. For examples of (S)-pyrrolidine sulfonamides promoted reactions,
see: (a) Wang, W.; Wang, J.; Li, H. Tetrahedron Lett. 2004, 45, 7235;
(b) Wang, W.; Wang, J.; Li, H. Tetrahedron Lett. 2004, 45, 7243; (c)
Wang, W.; Li, H.; Wang, J. Tetrahedron Lett. 2004, 45, 8229; (d)
Wang, W.; Wang, J.; Li, H. Angew. Chem., Int. Ed. 2005, 44, 1369; (e)
Wang, W.; Li, H.; Wang, J. Tetrahedron Lett. 2005, 46, 5077; (f)
Wang, J.; Li, H.; Mei, Y.; Lou, B.; Xu, D.; Xie, D.; Guo, H.; Wang,
W. J. Org. Chem. 2005, 70, 5678; (g) Wang, J.; Li, H.; Lou, B.; Zu,
L.-S.; Guo, H.; Wang, W. Eur. Chem. J. 2006, 12, 4321; (h) Wang, J.;
Li, H.; Zu, L.-S.; Wang, W. Adv. Synth. Catal. 2006, 348, 425; (i) Zu,
´
Cordova, A. Org. Biomol. Chem. 2006, 4, 38; (d) Huang, H.;
Jacobsen, E. N. J. Am. Chem. Soc. 2006, 128, 7170; (e) Lalonde, M.
P.; Chen, Y.; Jacobsen, E. N. Angew. Chem., Int. Ed. 2006, 45, 6366;
(f) Ramasastry, S. S. V.; Zhang, H.; Tanaka, F.; Barbas, C. F., III. J.
Am. Chem. Soc. 2007, 129, 288; (g) Chen, W.; Du, W.; Duan, Y.-Z.;
Wu, Y.; Yang, S.-Y.; Chen, Y.-C. Angew. Chem., Int. Ed. 2007, 46,
7667; (h) Xie, J.-W.; Chen, W.; Li, R.; Zeng, M.; Du, W.; Yue, L.;
Chen, Y.-C.; Wu, Y.; Zhu, J.; Deng, J.-G. Angew. Chem., Int. Ed.
2007, 46, 389.
9. See Supplementary data for the preparation of these organocatalysts
and some of them have been recently disclosed by other group during
our investigation: 1a,b reported in: (a) Tsogoeva, S. B.; Wei, S. W.
Chem. Commun. 2006, 1451; 1i reported in: (b) Shen, Z.-X.; Zhang,
Y.-Q.; Jiao, C.-J.; Li, B.; Ding, J.; Zhang, Y.-W. Chirality 2007, 19,
307; (c) Cao, C.-L.; Ye, M.-C.; Sun, X.-L.; Yang, Y. Org. Lett. 2006,
8, 2901.
10. Kano, T.; Takai, J.; Tokuda, O.; Maruoka, K. Angew. Chem., Int. Ed.
2005, 44, 3055.
25
20
11. ½aꢁD +85.4 (c 0.85, CHCl3) for 1m, lit.: ½aꢁD ꢀ85.3 (c 1.3, CHCl3) for
(S) enantiomer in: Mandal, S. K.; Jensen, D. R.; Pugsley, J. S.;
Sigman, M. S. J. Org. Chem. 2003, 68, 4600.