Asymmetric aldol reaction organocatalyzed by bifunctional N-prolyl sulfinamides under solvent-free conditions

Article abstract of DOI:10.1039/c4ra03362k

A class of chiral bifunctional N-prolyl sulfinamide and its TFA salts were prepared and proven to be effective for catalyzing the aldol reaction under solvent-free conditions. In general, the corresponding aldol adducts were obtained with high to excellen

Full text of DOI:10.1039/c4ra03362k

RSC Advances
View Article Online
View Journal | View Issue
PAPER
Asymmetric aldol reaction organocatalyzed by
bifunctional N-prolyl sulfinamides under
solvent-free conditions†
Cite this: RSC Adv., 2014, 4, 26563
a
a
a
b
a
a
a
Wen Wan,* Wei Gao, Guobin Ma, Lei Ma, Fan Wang, Jing Wang, Haizhen Jiang,
c
ac
Shizheng Zhu and Jian Hao*
A class of chiral bifunctional N-prolyl sulfinamide and its TFA salts were prepared and proven to be effective
for catalyzing the aldol reaction under solvent-free conditions. In general, the corresponding aldol adducts
were obtained with high to excellent yields, and satisfactory diastereo-selectivities and enantioselectivities.
A matching effect between chiral proline and sulfinamide moieties was observed in the catalysts. The
enantioswitching of both enantiomers in the asymmetric aldol synthesis is found to be dominated by the
prolyl moiety.
Received 14th April 2014
Accepted 30th May 2014
DOI: 10.1039/c4ra03362k
www.rsc.org/advances
molecules, since it provides the formation of new C–C bonds. In
past years, several solvent-free reaction conditions based on
Introduction
Since the pioneering work reported by B. List and co-workers in proline derivatives as organocatalysts have been developed in
1
2
000, the application of organocatalyzed protocols in asym- the direct aldol reaction, in order to overcome the drawbacks of
7
metric reactions has been well recognized due to the practical asymmetrical organocatalysis. At present, bifunctional activa-
advantages of these compared to transition-metal catalysed tion of both acceptor and donor has been widely accepted as an
2
procedures. Very recently, C. Sparr reported an organocatalytic important strategy in proline-catalyzed asymmetric aldol reac-
8
atroposelective aldol condensation, successfully providing tion. In this bifunctional catalysis, a nucleophilic enamine as a
3
axially chiral biaryls by arene formation. D. MacMillan donor is generated, while hydrogen bonding to the acceptor is
described an organocatalytic photoredox-based approach to the regarded as one of the criteria for the desired asymmetric
asymmetric a-amination of aldehydes via the direct coupling of induction. Following these principle approaches, new and effi-
4
functionalized nitrogen and formyl precursors. B. List devel- cient bifunctional organocatalysts by using various acidic N–H
oped a chiral disulfonimide organocatalyst in the efficient bonds of amides, sulfonamide and acylsulfonamides have been
9
asymmetric Mannich reaction of silyl ketene acetals with amino developed for asymmetric reactions. For example, E. Juaristi
5
sulfones. Though great progress in the organocatalytic asym- developed a dipeptide-type organocatalysts in the asymmetric
10
metric synthesis has been achieved in the past few years, most of aldol reaction under solvent-free conditions. T. Miura repor-
the asymmetric organocatalytic reactions are equilibrium ted efficient asymmetric aldol reaction catalyzed by a uorous
11
processes, which oen need a huge excess of reactant, high organocatalyst of b-aminosulfonamide.
catalyst loading, polar solvents and long reaction times. Thus, in
As part of our interest in developing bifunctional organo-
pursuit of a more efficient and environmentally friendly process, catalysts for environmentally-benign asymmetric processes,
the application of aqueous or solvent-free reaction conditions in herein we report a class of easily prepared, cheap, and ne
asymmetric organocatalyzed processes should be regarded as an tunable chiral bifunctional organocatalysts by combining two
6
improvement in the synthesis of complex molecules.
stereogenic centers to N-prolyl sulnamide. Additionally, the
The aldol reaction is one of the most powerful strategies in double chiral elements in this organocatalyst are also expected
the stereocontrolled preparation of small optically active to realize the asymmetric organocatalysis. These two stereo-
genic centers would act favourably (matched) or unfavourably
a
(mismatched) for stereocontrol of the desired prochiral
substrates in the asymmetric aldol reaction. The matched cases
Center for Drug Evaluation, State Food and Drug Administration, Beijing 100038, would lead to dramatically higher asymmetric induction in the
Department of Chemistry, Innovative Drug Research Center Shanghai University,
Shanghai 200444, China. E-mail: jhao@shu.edu.cn; wanwen@staff.shu.edu.cn
b
China
products. Meanwhile, an efficient enantioswitching of the
synthesized enantiomers is expected to be achieved through
the modication of chiral center of the organocatalyst. In this
context, four bifunctional organocatalysts of neutral N-prolyl
sulnamides 4a, its corresponding TFA salts 4b, 4c, and the
c
Key Laboratory of Organouorine Chemistry, Shanghai Institute of Organic
Chemistry, Chinese Academy of Sciences, Shanghai, China
†
Electronic supplementary information (ESI) available. CCDC 940363. For ESI
and crystallographic data in CIF or other electronic format see DOI:
0.1039/c4ra03362k
1
This journal is © The Royal Society of Chemistry 2014
RSC Adv., 2014, 4, 26563–26568 | 26563

View Article Online
RSC Advances
Paper
diastereoisomer 4d were prepared. Their applications in asym-
metric aldol reaction under solvent-free condition were
explored. In addition, attempts to develop methods of selec-
tively producing each one of the enantiomers with high enan-
tiomeric excess through asymmetric aldol reactions catalyzed by
enantiomeric or diastereoisomeric organocatalysts have also
been performed.
Results and discussion
Fig. 1 ORTEP drawing of X-ray crystal structure of 4b.
The synthetic procedures for catalysts 4a–4d are shown in
Scheme 1. The reaction of Boc-protected proline with R (or S)-
tert-butylsulnamide provided 3, which was then treated with
hydrochloric acid or triuoroacetic acid (TFA), through depro-
tecting the Boc-group to give neutral 4a in moderate yields.
Catalysts of TFA salts 4b, 4c and 4d were also synthesized for
comparison of their reactivity and efficiency. These compounds
were puried by ash column chromatography and character-
ized by H NMR, F NMR, C NMR spectra. All results were in
full agreement with the proposed structures. Following the
same procedure, these catalysts could be easily prepared on a
gram scale.
A colorless single crystal of organocatalyst 4b (ESI†) was
obtained by diffusion of hexane into its ethyl acetate solution
and the absolute stereochemistry was further conrmed by
single crystal X-ray diffraction analysis in order to elucidate its
molecular structure (Fig. 1). It is found that catalyst 4b has an
orthorhombic crystal lattice as shown from the XRD crystal
of the resulted adduct was determined by comparison of the
value of the optical rotation with that of previously described
0
12
and was found to (2S,1 R). A slight improvement of yield,
stereoselectivity was observed when a small amount of water
was added in the polar aprotic solvent of DMSO (entry 6).
Signicantly, excellent results of yield, diastereo- and enantio-
selectivity were achieved when solvent-free condition was
employed, in which the excess of ketone was limited to less than
1
19
13

ve equivalents (entry 7). Reducing the catalyst loading from 20
mol% to 0.5 mol% apparently affected the efficiency of the
reaction, resulting in the decrease of yield, and poorer dia-
stereo- and enantioselectivity, while maintaining the reaction
ꢀ
temperature at 25 C (entries 7–10). To our delight, the catalyst
performance was improved when decreasing the loading of the
catalyst to only 5 mol% and lowering the reaction temperature
ꢀ
ꢀ
from 25 C to 0 C, giving the best result of the aldol product 7a
in 96% yield with 98 : 2 anti/syn ratio and 96% ee value (entry
1
3
structure. There exist a CF COO/H–N hydrogen bonds
˚
(
2.774 A) between triuoroacetate anion and the pyrrolidine
1
1). As expected, the reaction required prolonged reaction time
˚
NH, and one amidic N–H/OCOCF hydrogen bond (2.725 A)
3
ꢀ
at 0 C. When the reaction temperature was further lowered
with the molecule stacked in the adjacent molecular stacking.
The tert-butyl group was placed far from the triuoroacetate.
Initially, the direct aldol reaction of cyclohexanone with
ꢀ
down to ꢁ10 C, an increase in reaction time of six days was
required without remarkable improvement of diastereo- and
enantioselectivity (entry 12). It was found that the reaction
became sluggish and the stereoselectivity was not improved
4-nitrobenzaldehyde catalyzed by 4b as a model process was
evaluated (Table 1). All reactions were carried out in the pres-
ence of 20 mol% of catalyst 4b at room temperature in different
solvents. Unfortunately, most reactions failed aer stirring for
several days even in the polar protic solvent of MeOH. To our
ꢀ
when the reaction temperature was further lowered to ꢁ20 C
(entry 13). The yield was sacriced remarkably and a much
prolonged reaction time was required to ensure a complete
ꢀ
ꢀ
conversion. Elevated reaction temperature from 0 C to 15 C
delight, the experiment in solvent of CH
2 2
Cl and DMSO, affor-
also decreased the reaction efficiency with only 86% ee value
ded the aldol adduct 7a in moderate yield with reasonable
1
(entry 14).
enantioselectivity (entries 4 and 5). The absolute conguration
Moreover, application of neutral catalyst 4a in the absence of
any Brønsted acid was also investigated in this solvent-free aldol
reaction. It was found that only reasonable enantioselectivity
with 82% ee value was presented in this condition (Table 1,
entry 15). Screening various Brønsted acids, such as HCl, HOAc,
3
CF COOH, Benzoic acid, p-toluenesulfonic acid, as a cocatalyst
with catalyst 4a in the solvent-free aldol reaction of cyclohexa-
none and p-nitrobenzaldehyde indicated that loading 5 mol%
TFA enabled the completion of the reaction in three day with
95% yield, and 94 : 6 dr, 95% ee.
Based on all of the above results, the scope of the solvent-
free aldol reaction of various aromatic benzaldehydes with
cyclohexanone was examined to test the substrate generality
(
Table 2). All reactions were performed in solvent-free system in
Scheme 1 Synthesis of N-prolyl sulfinamide 4a, TFA salts of 4b, 4c
and 4d.
presence of 5 to 10 mol% of catalyst either at ambient
26564 | RSC Adv., 2014, 4, 26563–26568
This journal is © The Royal Society of Chemistry 2014

View Article Online
Paper
RSC Advances
a
Table 1 Optimization of reaction conditions between cyclohexanone and p-nitrobenzaldehyde
c
d
e
f
Entry
Solvent
Catalyst (mol %)
Time (day)
Yield (%)
dr anti/syn
ee (%)
1
2
3
4
5
6
7
8
9
Toluene
20
20
20
20
20
20
20
10
1
1
1
1
1
1
1
1
1
2
2
3.5
6
6
Trace
Trace
Trace
75
70
93
98
92
92
60
—
—
—
—
—
—
—
68
75
80
94
89
89
83
96
96
96
86
82
CH
THF
CH Cl
3
OH
2
2
DMSO
DMSO/H
Neat
Neat
Neat
90 : 10
93 : 7
95 : 5
94 : 6
92 : 8
89 : 11
98 : 2
98 : 2
98 : 2
94 : 6
86 : 14
2
O (10/1)
10
11
12
13
14
15
Neatb
0.5
5
5
ꢀ
Neat (0 C)
97
90
40
98
b
ꢀ
ꢀ
Neat (ꢁ10 C)
b
Neat (ꢁ20 C)
5
b
ꢀ
Neat (15 C)
5
5
1
3
b
ꢀ
g
Neat (0 C)
97
a
ꢀ
Unless otherwise stated, reaction conditions were as follows: cyclohexanone (2.5 mmol), p-nitrobenzaldehyde (0.5 mmol), temperature (25 C),
b
c
d
e
1
and indicated solvents. Reaction at indicated temperature. Catalyst 4b for indicated loading. Isolated yield. Determined by H NMR of the
crude product. Determined by chiral-phase HPLC analysis for the anti isomer. Reaction conducted with catalyst 4a.
f
g
ꢀ
temperature or at 0 C. The nitro, cyano, triuoromethyl, uoro, ee value (entries 10 and 11). In general, very similar results are
were chosen as electron-withdrawing groups, and the furanyl obtained for the enantiomeric aldol adducts, including the
substituent as representative electron-donating group. It could yields, de and ee values which are within the experimental
be seen that a wide range of aromatic aldehydes effectively errors, when the enantiomeric catalysts of 4b and 4c were
participated in the aldol reaction, and both enantiomers of applied in the reactions.
aldol adducts 7a–7k derived from their corresponding aromatic
To compare the catalytic efficiency and selectivity of the two
aldehydes and cyclohexanone could be accessed, when enan- diastereomeric catalytic systems of 4b (or 4c) with 4d, we further
tiomeric catalysts (S,R)-4b and (R,S)-4c were applied in this examined the asymmetric reaction of representative substrates
direct aldol reaction. In all cases, the anti aldol products were of 5a–5f with cyclohexanone catalyzed by 4d in the model
obtained as major isomers and the chemical yield, diastereo- solvent-free aldol reaction (Table 3). Disappointingly, much
and enantioselectivity, and the reaction rates were found to poorer enantioselectivities and prolonged reaction times were
obviously depend upon the position and nature of the substit- presented with catalyst (R,R)-4d, compared with those catalyzed
uents on the aromatic moiety.
by its diastereoisomers (S,R)-4b or (R,S)-4c. As is shown in
It was appreciated in Table 2 that benzaldehydes substituted Table 2, the enantiomeric catalysts (S,R)-4b and (R,S)-4c affor-
by electron-withdrawing groups, such as nitro, cyano, could be ded much higher activities and enantioselectivities under the
converted to the corresponding anti-aldol products in moderate same reaction conditions.
to high yields and enantioselectivities, the latter within 87–98%
When studying the aldol reaction catalyzed by diastereoiso-
ee range (entries 1–9). Excellent enantioselectivity (ee 98%) mers of (S,R)-4b and (R,R)-4d, it was found that a pair of enan-
0
0
and diastereoselectivity (anti/syn > 99 : 1) were observed when tiomers of aldol adducts (2S,1 R) and (2R,1 S) were afforded,
-nitrobenzaldehyde was employed as the acceptor (entry 2). respectively. A reversed sense of asymmetric induction was
3
The products 7d, 7e and 7f (entries 4–6) bearing cyano, triuoro presented, indicating that switching conguration of prolyl
or 2,4-dichloro substitution were obtained in comparable moiety from S to R mainly provided the stereochemical control
selectivity with those of aldol adducts with nitro substitution. of the reaction. These results indicated that, an efficient enan-
The reaction of 4-bromo and 4-chloro benzaldehydes with tioswitching of the aldol adducts could be achieved through the
cyclohexanone gave the aldol adducts 7g and 7h in moderate modication of the prolyl structure.
0
yields with good enantioselectivities (entries 7 and 8). In some
Another important nding was that the same (2R,1 S)-
cases, the 10 mol% of catalyst loading was applied in order to enantiomer of the product was formed when diastereoisomeric
improve the reactivities (entries 5–8). On the other hand, use of catalyst (R,S)-4c or (R,R)-4d was applied, regardless of their
the less reactive substrate of benzaldehyde, such as 5j, hetero- overall backbone, suggesting that the chirality of prolinamide
cyclic 2-furaldehyde 5k, provided moderate yield and acceptable backbone overrides the other bias imposed by the sulnyl
This journal is © The Royal Society of Chemistry 2014
RSC Adv., 2014, 4, 26563–26568 | 26565

View Article Online
RSC Advances
Paper
a
Table 2 Aldol reaction of cyclohexanone with substituted benzaldehydes under solvent-free conditions
b
c
d
Entry
ArCHO
Product
Catalyst (mol%)
Time (day)
Yield (%)
dr anti/syn
ee (%)
e
1
2
3
4
5
6
7
8
4-NO
3-NO
2-NO
2
2
2
C
C
C
6
6
6
H
H
H
4
4
4
5a
5b
5c
7a
1
5
3.5
3.5
5
5
5
5
5
5
4
4
6
6
6
6
6
6
6
97
95
94
92
95
93
95
95
66
71
66
70
53
45
40
38
45
50
80
83
70
62
98 : 2
>99 : 1
>99 : 1
>99 : 1
>99 : 1
95 : 5
96 : 4
97 : 3
95 : 5
92 : 8
90 : 10
89 : 11
97 : 3
96 : 4
96 : 4
97 : 3
95 : 5
94 : 6
91 : 9
90 : 10
66 : 34
68 : 32
96
94
98
94
96
90
95
92
94
94
93
94
91
90
89
87
93
90
74
69
57
54
f
7a
2
5
e
7b
1
5
f
7b
2
5
e
7c
1
5
f
7c
2
5
e
4-CNC
4-CF
2, 4-ClC
4-BrC
4-ClC
6
H
4
5d
5e
H 5f
7d
1
5
f
7d
2
5
e
3
C
6
H
4
7e
1
10
f
7e
2
10
e
6
7f
1
10
f
7f
2
10
e
6
H
4
5g
5h
7g
1
2
10
f
7g
10
e
6
H
4
7h
1
10
f
7h
2
10
e
9
2-Naphthyl 5i
4-HC 5j
2-Furanyl 5k
7i
1
10
f
7
7j
i
2
1
2
10
6
6
6
6
g
e
1
1
0
6
H
4
10
f
7j
10
g
e
1
7k
1
10
f
7k
2
10
6
a
The reaction were performed with 0.5 mmol of aldehyde, 2.5 mmol of cyclohexanone, in the presence of organocatalyst as indicated loading at
ꢀ
b
c
1
d
temperature of 0 C. Isolated yield. Determined by H NMR of the crude product. Determined by chiral-phase HPLC analysis for the anti
isomer. The reaction was performed in the presence of catalyst 4b. The reaction was performed in the presence of catalyst 4c. The reaction
were performed in the presence of organocatalyst as indicated loading at temperature of 25 C.
e
f
g
ꢀ
skeleton chirality. The conguration of the enantiomer of the catalyzed by (R,S)-4c. However, R-conguration of prolyl moiety
aldol adduct is predominated by prolyl moiety. This unique mismatched the R-conguration of sulnyl moiety in catalyst of
chiral environment with R-conguration of prolyl moiety and S- (R, R)-4d, resulting in relatively low catalytic activity and low
conguration of sulnyl moiety may act as suitably matching enantioselectivity.
effect, which would be attributed to the higher catalytic activi-
Compared with bifunctional organocatalyst of (S)-N-
ties and enantio-selectivities obtained in this aldol reactions (methylsulfonyl) pyrrolidine-2-carboxamide which possesses
a
Table 3 Studies of aldol reaction with catalyst 4d
b
c
d
Entry
ArCHO
Product
7a
Catalyst (mol%)
Time (day)
Yield (%)
dr anti/syn
ee (%)
1
2
3
4
5
4-NO
3-NO
2
C
C
6
H
H
4
5a
5b
5d
5e
5f
2
5
5
5
10
10
5
5
5
5
5
88
50
32
25
34
90 : 10
82 : 18
67 : 33
70 : 30
73 : 27
38
65
33
49
42
2
6
4
7b
7d
2
4-CNC
4-CF
2, 4-ClC
6
H
4
2
3
C
6
H
4
7e
7f
2
6
H
4
2
a
The reaction were performed with 0.5 mmol of aldehyde, 2.5 mmol of cyclohexanone, in the presence of catalyst 4d as indicated loading at
ꢀ
b
c
1
d
temperature of 0 C. Isolated yield. Determined by H NMR of the crude product. Determined by chiral-phase HPLC analysis for anti isomer.
26566 | RSC Adv., 2014, 4, 26563–26568
This journal is © The Royal Society of Chemistry 2014

View Article Online
Paper
RSC Advances
only one stereogenic center derived from chiral proline moiety, sulnamide 4a–4d in this work, we propose that the N-prolyl
the (S, R)-N-prolyl sulnamide 4a or its TFA salts (S,R)-4b sulnamide catalyst could catalyze the direct aldol reaction via
synthesized in this work provided an additional chiral center the plausible transition state shown in Fig. 2.
from sulnamide moiety. In contrast to the asymmetric direct
The pyrrolidine moiety in bifunctional organocatalyst 4b
aldol reaction catalyzed by (S)-N-(methylsulfonyl) pyrrolidine-2- reacts with cyclohexanone to form nucleophilic enamine. The
carboxamide, in which moderate yield and enantioselectivity carbonyl group of the aldehyde could be greatly activated by
13
were observed, the aldol reaction in this work proceed well hydrogen bonding with amide proton of the prolinamide unit of
through the doubly stereocontrolled organocatalyst 4b, afford- the catalyst 4b, because of the inductive electron-withdrawing
ing high to excellent yield, satisfactory diastereo-selectivities effect of the sulnyl group, which can remarkably acidify the N–
and enantioselectivities. These results indicated that the H bond. The tert-butyl group is located far from the reaction
introduction of the additional stereogenic center of the sul- center, due to its strong steric hindrance. Thus, the favoured
namide moiety (S) to the matched proline (R) would apparently transition-state, TS1 is predicted in Fig. 2. On the other hand,
improve the diastereo- and enantioselectivity in the asymmetric the phenyl group of benzaldehyde has a severe steric interaction
aldol reaction.
with tert-butyl group, presenting the unfavoured transition-
Finally, the feasibility of using other cyclic and acyclic state TS2 (Fig. 2). The approach of the aldehyde in the favour-
ketones as aldol donors using 4b as catalyst was investigated. As able TS1 is facile and the enantioselective C–C bond formation
0
shown in Table 4, acyclic acetone 8a provided moderate enan- takes places on the re-face of the aldehyde, leading to (2S,1 R)-
tioselectivity and yield along with prolonged reaction time isomer.
(entry 1). In case of cyclic ketone having ve membered ring,
Meanwhile, the attractive interaction between the electron
cyclopentanone 8b provided high yield with moderate diaster- pair from chiral sulnyl group and the electron-decient
eoselectivity and reasonable enantioselectivity under the model aromatic ring, which contains strong electron-withdrawing
reaction condition (entry 2). Lowering the reaction temperature substituents, such as NO
2
-, 2,4-dichloro-, can also stabilize the
ꢀ
down to ꢁ20 C gave poor yield and prolonged reaction time favoured transition state of TS1. As a result, much higher ee
required, without remarkable improvement of enantiose- values were obtained in this work when benzaldehydes
lectivity (entry 3). Cycloheptanone 8c having seven membered substituted by strong electron-withdrawing groups were
ring afforded much poor reactivity, which resulted in much applied. However, benzaldehydes with electron-donating
ꢀ
lower yield even at higher reaction temperature of 25 C and
with more catalyst loading. It only provided moderate diastereo-
and low enantioselectivity (entry 4).
An unexpected reversal of the diastereoselectivity was
observed in the case of cyclopentanone (Table 4, entry 2), in
which the syn product was found to be the predominant dia-
stereomer, In all cases, the reactions in this work provided
reasonable to high anti stereoselectivity except cyclopentanone
14
applied in this aldol reactions.
The possible mechanism in the aldol reaction catalyzed by
proline and its derivatives has been extensively discussed, with
15
the enamine formation being assumed. To account for the
Fig. 2 Proposed transition state for the aldol reaction of cyclo-hex-
stereochemical outcome of our study catalyzed by N-prolyl anone catalyzed by (S,R)-4b.
a
Table 4 Aldol reaction of acyclic or cyclic ketones with 4-nitrobenzaldehyde under solvent-free conditions
b
c
d
Entry
R
1
R
2
Product
7l
Catalyst (mol%)
Time (day)
Yield (%)
dr anti/syn
ee (%)
1
2
3
4
CH
3
–8a
H
1
5
5
6
2.5
6
40
95
43
45
86 : 14
36 : 64
35 : 65
70 : 30
50
74
81
36
–(CH
–(CH
–(CH
2
)
2
)
2
)
3
3
5
–8b
–8b
–8c
7m
7m
1
e
1
5
f
7n
1
10
6
a
The reaction were performed with 0.5 mmol of aldehyde, 2.5 mmol of cyclohexanone, in the presence of catalyst 4b as indicated loading at
ꢀ
b
c
1
d
temperature of 0 C. Isolated yield. Determined by H NMR of the crude product. Determined by chiral-phase HPLC analysis for the major
isomer. At temperature of ꢁ20 C. At temperature of 25 C.
e
ꢀ
f
ꢀ
This journal is © The Royal Society of Chemistry 2014
RSC Adv., 2014, 4, 26563–26568 | 26567

View Article Online
RSC Advances
Paper
groups only afforded lower enantioselectivities in this aldol
reaction, due to the repulsive interaction in TS1 between the
electron-rich aromatic ring and the electron pair from chiral
sulnyl group.
G. Nicholas, Handbook of Green Chemistry, Wiley-VCH,
Weinheim, 2012; (d) R. A. Sheldon, Chem. Soc. Rev., 2012,
41, 1437.
7 (a) G. Gabriela, M. C. Hita, C. Najera and S. F. Viozquez,
J. Org. Chem., 2008, 73, 5933; (b) D. Almasi, D. A. Alonso,
A. N. Balaguer and C. Najera, Adv. Synth. Catal., 2009, 351,
Conclusions
1123; (c) A. Banon-Caballero, G. Guillena and C. Najera,
In summary, bifunctional N-prolyl sulnamide and TFA as co-
catalyst were applied in catalytic reaction under solvent-free
conditions. The aldol products were obtained with high to
excellent yield, diastereo- and enantioselectivities. The selec-
tivity data revealed that the matched system in catalysts (S,R)-4b
or (R,S)-4c afforded much higher yield and enantioselectivity, in
contrast to their diastereoisomer of (R,R)-4d. The presence of
the chiral prolyl scaffold within the backbone of the catalysts
predominates the conguration of the aldol adducts. An effi-
cient chirality switching in the asymmetric aldol addition was
presented through the modication of the conguration of the
prolyl moiety.
Green Chem., 2010, 12, 1599; (d) A. Martinez-Castaneda,
B. Poladura, H. Rodriguez-Solla and C. V. Concellon, Org.
Lett., 2011, 13, 3032; (e) A. Martinez-Castaneda,
B. Poladura, H. Rodriguez-Solla, C. Concellon and V. del
Amo, Chem.–Eur. J., 2012, 18, 5188; (f) J. G. Hernandez and
E. Juaristi, Chem. Commun., 2012, 48, 5396.
8 (a) B. Rodriguez, T. Rantanen and C. Bolm, Angew. Chem.,
Int. Ed., 2006, 45, 6924; (b) H. S. Rho, J. W. Lee, J. E. Lee,
S. H. Youk, J. Chin and C. E. Song, Angew. Chem., 2008, 47,
7872; (c) C. Rabalakos and W. D. Wulff, J. Am. Chem. Soc.,
2008, 130, 13524; (d) X. H. Liu, L. L. Lin and X. M. Feng,
Chem. Commun., 2009, 6145; (e) M. Fochi, L. Gramigna,
A. Mazzanti, S. Duce, S. Fantini, A. Palmieri, M. Petrini and
L. Bernardi, Adv. Synth. Catal., 2012, 354, 1373; (f)
S. Anwar, P. H. Lee, T. Y. Chou, C. Chang and K. Chen,
Tetrahedron, 2011, 67, 1171.
Acknowledgements
This work was nancially supported by the National Natural
Science Foundation of China (no. 21172141, 21072127,
9
(a) Z. Tang, Z. H. Yang, X. H. Chen, L. F. Cun, A. Q. Mi,
Y. Z. Jiang and L. Z. Gong, J. Am. Chem. Soc., 2005, 127,
21032006, 20132121). Dr Hongmei Deng (Department Labora-
tory for Microstructures, Shanghai University) was thanked for
helping with use of the NMR facility.
9
285; (b) A. Cobb, D. M. Shaw, D. A. Longbottom,
J. B. Gold and S. V. Ley, Org. Biomol. Chem., 2005, 3, 84; (c)
H. Yang and R. G. Carter, Synlett, 2010, 19, 2827; (d)
M. T. Robak, M. A. Herbage and J. A. Ellman, Tetrahedron,
Notes and references
2011, 67, 4412; (e) R. Somanathan, D. Chavez, F. A. Servin,
1
(a) B. List, R. A. Lerner and C. F. Barbas, J. Am. Chem. Soc.,
000, 122, 2395; (b) K. Sakthivel, W. Notz, T. Bui and
A. Romero, A. Navarrete, M. P. Hake, G. Aguirre,
P. C. Anaya and J. Gonzalez, Curr. Org. Chem., 2012, 16, 2440.
0 J. G. Hern ´a ndez and E. Juaristi, J. Org. Chem., 2011, 76, 1464.
1 T. Miura, H. Kaasuga, K. Imai, M. Ina, N. Tada, N. Imaib and
A. Itoha, Org. Biomol. Chem., 2012, 10, 2209.
2 A. Karmakar, T. Maji, S. Wittmann and O. Reiser, Chem.–Eur.
J., 2011, 17, 11024.
3 A. J. A. Cobb, D. M. Shaw, D. A. Longbottom, J. B. Golda and
S. V. Ley, Org. Biomol. Chem., 2005, 3, 84.
4 (a) S. Saito and H. Yamamoto, Acc. Chem. Res., 2004, 37, 570;
2
C. F. Barbas, J. Am. Chem. Soc., 2001, 123, 5260.
1
1
2
For reviews on organocatalysis, see: (a) A. Berkessel and
H. Groger, Asymmetric Organocatalysis, Wiley-VCH,
Weinheim, 2005; (b) P. I. Dalko, Enantioselective
1
1
1
Organocatalysis,
Wiley-VCH,
Weinheim,
2007;
(c)
S. Mukherjee, J. W. Yang, S. Hoffmann and B. List, Chem.
Rev., 2007, 107, 5471; (d) M. M. Heravi and S. Asadi,
Tetrahedron: Asymmetry, 2012, 23, 1431; (e) H. Pellissier,
Adv. Synth. Catal., 2012, 354, 237.
(
b) M. Arno, R. J. Zaragoza and L. R. Domingo, Tetrahedron:
3
4
A. Link and C. Sparr, Angew. Chem., Int. Ed., 2014, 53, 5458.
G. Cecere, C. M. K ¨o nig, J. L. Alleva and D. W. C. MacMillan,
J. Am. Chem. Soc., 2013, 135, 11521.
Asymmetry, 2005, 16, 2764; (c) X. H. Chen, S. W. Luo, Z. Tang,
L. F. Cun, A. Q. Mi, Y. Z. Jiang and L. Z. Gong, Chem.–Eur. J.,
2
Adv. Synth. Catal., 2009, 351, 33; (e) S. Saha and
J. N. Moorthy, Tetrahedron Lett., 2010, 51, 912.
5 S. Fotaras, C. Kokotos, E. Tsandi and G. Kokotos, Eur. J. Org.
Chem., 2011, 7, 1310.
007, 13, 689; (d) M. Gruttadauria, F. Giacalone and R. Noto,
5
6
Q. Wang, M. Leutzsch, M. Gemmeren and B. List, J. Am.
Chem. Soc., 2013, 135, 15334.
(a) P. T. Anastas and J. C. Warner, Green Chemistry: Theory
and Practice, Oxford University Press, Oxford, 1998; (b)
K. Tanaka, Solvent-free Organic Synthesis, Wiley-VCH,
Weinheim, 2003; (c) I. Beadham, G. Monika and
1
26568 | RSC Adv., 2014, 4, 26563–26568
This journal is © The Royal Society of Chemistry 2014