One-pot asymmetric synthesis of 2-aryl-2,3-dihydro-4-quinolones catalyzed by amino acid-derived sulfonamides

Article abstract of DOI:10.1016/j.tetasy.2013.05.028

An organocatalyzed approach to the asymmetric synthesis of 2-aryl-2,3-dihydro-4-quinolones using amino-acid derived sulfonamides as organocatalysts, which can be easily prepared starting from l-proline, l-alanine, and l-phenylalanine, has been developed i

Full text of DOI:10.1016/j.tetasy.2013.05.028

Tetrahedron: Asymmetry 24 (2013) 875–882
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Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
One-pot asymmetric synthesis of 2-aryl-2,3-dihydro-4-quinolones
catalyzed by amino acid-derived sulfonamides
⇑
⇑
Haixing Zheng, Qi Liu, Saishuai Wen, Hua Yang , Yiming Luo
School of Chemistry and Chemical Engineering, Central South University, Changsha 410083, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
An organocatalyzed approach to the asymmetric synthesis of 2-aryl-2,3-dihydro-4-quinolones using
amino-acid derived sulfonamides as organocatalysts, which can be easily prepared starting from -pro-
line, -alanine, and -phenylalanine, has been developed in high yields (up to 92%) and with moderate
to good enantioselectivities (up to 74% ee). Additionally, opposite enantioselectivities for primary and
secondary amino acid sulfonamides have also been observed.
Received 18 April 2013
Accepted 28 May 2013
Available online 26 July 2013
L
L
L
Ó 2013 Elsevier Ltd. All rights reserved.
1. Introduction
transition-metal-mediated catalytic processes and obtained high
yields and enantioselectivities. Lu et al.22c obtained high yields
The asymmetric Mannich reaction is one of the most important
carbon–carbon bond and carbon–nitrogen bond forming reactions
for the synthesis of optically active nitrogen-containing mole-
cules.1,2 The resulting chiral b-amino carbonyl compounds are
valuable precursors in the preparation of many natural products
and drugs. The products of the Mannich reaction can often be read-
ily converted into various compounds with useful biological and
pharmaceutical properties. Traditionally, asymmetric Mannich
reactions are catalyzed by chiral transition-metal complexes.3–5
In 2000, List et al. reported on the first direct asymmetric three-
component Mannich reaction between an aldehyde, p-methoxyan-
and excellent enantioselectivities by using bifunctional thiourea
catalysts instead of metal catalysts, while including multiple steps
for the activation and removal of activating groups. Recently, Pitc-
humani et al.22d reported on a one-pot asymmetric synthesis of
2-aryl-2,3-dihydro-4-quinolones catalyzed by per-6-amino-b-
cyclodextrin in high yields and enantioselectivities. However, the
cyclodextrins were biological macromolecules, which are unstable
and difficult to modify to become catalytically active substances.
Taking all of these reports into account, the employment of simple
organic molecules as organocatalysts, which could not only pro-
duce less waste but also avoid complicated separation and purifi-
cation protocols, is highly desirable.
iline (p-anisidine) and a ketone catalyzed by L
-proline.6,7 This land-
mark research stimulated the rapid development of many
asymmetric organocatalytic Mannich reactions.8–14 Typically, an
organocatalytic approach to an asymmetric Mannich reaction is
based on enamine activation of carbonyl compounds using second-
ary amine (pyrrolidine amide) organocatalysts.15,16 Other types of
organocatalysts such as chiral Brønsted acids,17 cinchona alka-
loids,18 or phase-transfer catalysts19 have also been successfully
used for Mannich-type reactions.
2-Aryl-2,3-dihydro-4-quinolones, which can be considered as
aza-analogues of flavanones, have demonstrated a wide range of
biological activities and pharmaceutical properties as anticancer
and antibiotic agents.20,21 Since individual enantiomers of quino-
lones have different biological activities, it is highly desirable to de-
velop enantioselective methods to access this class of important
antibiotics. To the best of our knowledge, only five articles have
so far been reported for the synthesis of enantioenriched 2-aryl-
2,3-dihydro-4-quinolones. Hayashi22a and Hou22b made use of
In 2007, Chandrasekhar et al. reported on a proline-catalyzed
one-pot synthesis of 2-aryl-2,3-dihydro-4-quinolones from the
intramolecular Mannich reaction of aldehydes with 2-aminoaceto-
phenone,22e with good yields being obtained. However, poor
enantioselectivity (17% ee) was observed. Inspired by this finding,
we designed and synthesized a series of new sulfonamide organo-
catalysts, which were expected to facilitate the reaction to prepare
2-aryl-2,3-dihydro-4-quinolones in high enantioselectivity and
yield. Herein we report application of the amino acid-derived sul-
fonamides to catalyze the one-pot asymmetric synthesis of 2-aryl-
2,3-dihydro-4-quinolones.
2. Results and discussion
Preliminary studies were conducted on 2-aminoacetophenone 1
and benzaldehyde 2 utilizing sulfonamide organocatalysts (Ta-
ble 1). Catalysts 4a–i used herein were easily prepared from the
coupling reactions between the Boc-protected amino acids and
the corresponding sulfonamides followed by deprotection.23
⇑
Corresponding authors. Tel.: +86 731 88830833; tel.: +86 731 88864409.
E-mail addresses: hyangchem@csu.edu.cn (H. Yang), ymluo@csu.edu.cn (Y. Luo).
0957-4166/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetasy.2013.05.028

876
H. Zheng et al. / Tetrahedron: Asymmetry 24 (2013) 875–882
Table 1
Screening of catalysts for the asymmetric synthesis of 2-aryl-2,3-dihydro-4-quinolonesa
O
O
O
CHO
10 mol% catalyst 4
+
+
CH2Cl2, rt
NH2
N
H
N
H
1
2
3a
3a'
O
O
O
O
S
O
S
O
S
catalyst:
N
H
HN
N
H
HN
N
H
HN
C12H25
O
O
O
4c
4b
4a
O
S
O
O
S
H
N
H
N
H
N
C12H25
S
H2N
H2N
H2N
O
O
O
O
O
O
4f
4d
4e
O
O
S
O
S
H
H
N
H
N
S
C12H25
N
H2N
H2N
H2N
O
O
O
O
O
4i
O
4g
4h
Entry
Catalyst
Solvent
Yieldb (%)
eec,d (%)
1
2
3
4
5
6
7
8
9
4a
4b
4c
4d
4e
4f
4g
4h
4i
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
85
72
72
84
74
78
68
60
62
22
14
12
ꢀ25
ꢀ13
ꢀ12
ꢀ16
ꢀ11
ꢀ13
a
Reaction conditions: 2-aminoacetophenone 1 (1.0 mmol), benzaldehyde 2 (1.5 mmol), catalyst 4a–i (0.1 mmol), solvent (CH2Cl2, 1 mL), room temperature (25 °C), and
reaction time (48 h).
b
Yield of the isolated product after chromatography.
c
Determined by chiral HPLC analysis (Chiralcel OD-H column).
d
Absolute configurations were assigned through comparison of the specific rotations with literature data.22a–d
Initially, all of the reactions were performed under the condi-
tions of 2-aminoacetophenone 1 (1.0 equiv) with benzaldehyde 2
(1.5 equiv) in the presence of 10 mol % catalyst 4a–i in dichloro-
methane (CH2Cl2) at room temperature. Amongst the catalytic sys-
tems tested (Table 1), catalytic activities varied significantly. These
organocatalysts 4a–i exhibited good catalytic reactivity for this
reaction (entries 1–9) in good yields (62–85%) within 48 h. The pri-
mary amine and secondary amine catalysts showed the opposite
stereoselectivities for this transformation although these organo-
catalysts 4a–i exhibited unsatisfactory enantioselectivities (11–
25% ee). The proline sulfonamide catalyst 4a and the primary
amine sulfonamide catalyst 4d provided superior catalytic activi-
ties in good yields (85% and 84%), and reasonable enantioselectiv-
ities (22% ee and ꢀ25% ee) respectively. It was observed that the
introduction of a methyl group at the ortho-position of the sulfon-
amide in the catalyst structure provided the highest enantioselec-
tivity. The existence of a more sterically demanding group such as
an iso-propyl group, leads to a decrease in enantioselectivity. The
proline sulfonamide derivative (2S)-N-(p-dodecylphenylsulfonyl)-
2-pyrrolidinecarboxamide, nicknamed as ‘Hua Cat’, showed
inferior enantioselectivity. As for the primary amino acid derived
sulfonamides, the alanine-derived sulfonamides gave compara-
tively higher chemical yields and enantioselectivities than the
phenylalanine series. Presumably, the presence of a benzene ring
in the phenylalanine interfered with the interaction between the
catalyst and the substrate. Subsequently, catalyst 4a and catalyst
4d were selected for further optimization to improve the enanti-
oselectivity of this transformation.
Next, several typical organic solvents (Table 2, entries 1–9)
were screened in the presence of 10 mol % 4a or 4d. As shown in
Table 2, the reaction yields and enantioselectivities were highly
solvent dependent. Lower enantioselectivities were obtained when
less polar aprotic solvents were used (entries 1–5). More polar sol-
vents afforded the adduct 3 in significantly improved yields (en-
tries 6 and 7). High yields (92%, 90%, entry 7) and moderate
enantioselectivities (30% ee, ꢀ35% ee, entry 7) were achieved in

H. Zheng et al. / Tetrahedron: Asymmetry 24 (2013) 875–882
877
Table 2
Screening of solvents for the asymmetric synthesis of 2-aryl-2,3-dihydro-4-quinolones catalyzed by organocatalyst 4a or 4da
O
O
O
CHO
10 mol% catalyst
solvent, rt
+
+
NH2
N
H
N
H
1
2
3a
3a'
Entry
Solvent
Catalyst 4a
Catalyst 4d
Yieldb (%)
eec,d (%)
Yieldb (%)
eec,d (%)
1
2
3
4
5
6
7
8
CH2Cl2
CHCl3
Toluene
THF
MeCN
DMF
DMSO
i-PrOH
MeOH
H2O
85
80
75
77
62
90
92
65
79
21
17
22
25
26
32
38
25
30
42
45
12
14
84
82
74
72
61
89
90
63
79
24
15
ꢀ25
ꢀ20
ꢀ23
ꢀ35
ꢀ41
ꢀ32
ꢀ35
ꢀ43
ꢀ51
ꢀ14
ꢀ16
9
10
11
Brine
a
Reaction conditions: 2-aminoacetophenone 1 (1.0 mmol), benzaldehyde 2 (1.5 mmol), catalyst 4a or 4d (0.1 mmol), solvent (1 mL), room temperature (25 °C), and
reaction time (48 h).
b
Yield of the isolated product after chromatography.
c
Determined by chiral HPLC analysis (Chiralcel OD-H column).
d
Absolute configurations were assigned by comparison of the specific rotations and chiral chromatography with literature data.22a–d
Table 3
Screening of the reaction temperature for the asymmetric synthesis of 2-aryl-2,3-dihydro-4-quinolones catalyzed by organocatalyst 4a or 4da
O
O
O
CHO
10 mol% catalyst
CH3OH
+
+
NH2
N
H
N
H
1
2
3a
3a'
Entry
Catalysta
T (°C)
Time (h)
Yieldb (%)
eec,d (%)
1
2
3
4
5
6
7
8
4a
4a
4a
4a
4d
4d
4d
4d
25
0
ꢀ20
ꢀ40
25
24
48
72
72
24
48
72
72
79
76
68
45
76
70
63
38
45
52
65
68
ꢀ51
ꢀ56
ꢀ70
ꢀ72
0
ꢀ20
ꢀ40
a
b
c
Reaction conditions: 2-aminoacetophenone 1 (1.0 mmol), benzaldehyde 2 (1.5 mmol), catalyst 4a or 4d (0.1 mmol), and solvent (MeOH, 1 mL).
Yield of the isolated product after chromatography.
Determined by chiral HPLC analysis (Chiralcel OD-H column).
d
Absolute configurations were assigned by comparison of the specific rotations and chiral chromatography with the literature data.22a–d
DMSO (analytic grade). Protic organic solvents such as i-PrOH and
MeOH seemed to have a beneficial effect on the enantioselectivity
(entries 8 and 9). We found that MeOH was the most suitable or-
ganic solvent (entry 9). The corresponding product 3 was obtained
in moderate yields with the highest enantioselectivity (45% ee,
ꢀ51% ee) in MeOH. The water compatible behavior of catalysts
4a and 4d was also tested. However, only a small amount of the de-
sired product was obtained in water or brine and the enantioselec-
tivities were poor (entries 10 and 11, Table 2). Therefore, MeOH
was chosen as the solvent for subsequent tests.
enantioselectivity increased from 45% to 65% for 4a and ꢀ51% to
ꢀ70% for 4d without a loss of chemical yield (Table 3, entries 3
and 7). Lowering the reaction temperature further (ꢀ40 °C) led to
sluggish reaction but improved the enantioselectivities slightly.
Taking into account the reactivity and enantioselectivity, ꢀ20 °C
was considered to be the optimal reaction temperature.
Catalyst loading is usually an important issue in organocatalytic
reactions. For instance, L-proline is typically used at approximately
20 mol %. As shown in Table 4, when the catalyst loading was less
than 20 mol % of 4a or 4d, it led to prolonged reaction times and
reduced chemical yields (entries 3–4 and 7–8). On the other hand,
a higher catalyst loading (30 mol %) provided similar results com-
pared to 20 mol % of catalyst loading for catalyst 4a or 4d (entries
The reaction temperature was also screened for this transforma-
tion in order to improve the enantioselectivity further. By decreas-
ing the reaction temperature from room temperature to ꢀ20 °C, the

878
H. Zheng et al. / Tetrahedron: Asymmetry 24 (2013) 875–882
Table 4
Screening of the catalyst loading for the asymmetric synthesis of 2-aryl-2,3-dihydro-4-quinolones catalyzed by organocatalyst 4a or 4da
O
O
O
CHO
catalyst
+
+
MeOH, -20oC
NH2
N
H
N
H
1
2
3a
3a'
Entry
Catalyst
Catalyst loading (mol %)
Time (h)
Yieldb (%)
eec,d (%)
1
2
3
4
5
6
7
8
4a
4a
4a
4a
4d
4d
4d
4d
30
20
10
5
30
20
10
5
14
20
48
72
16
22
48
72
83
82
65
53
79
72
60
50
65
65
65
63
ꢀ70
ꢀ70
ꢀ70
ꢀ69
a
b
c
Reaction conditions: 2-aminoacetophenone 1 (1.0 mmol), benzaldehyde 2 (1.5 mmol), solvent (MeOH, 1 mL), and reaction temperature (ꢀ20 °C).
Yield of the isolated product after chromatography.
Determined by chiral HPLC analysis (Chiralcel OD-H column).
d
Absolute configurations were assigned by comparison of the specific rotations and chiral chromatography with the literature data.22a–d
1–2 and 5–6). Therefore, 20 mol % catalyst loading for 4a and 4d
was applied in our continued investigation of this transformation.
The reaction scope was explored under the optimized condi-
tions (20 mol % of catalyst in MeOH at ꢀ20 °C) for catalysts 4a
and 4d. The results are summarized in Table 5. The substrate toler-
ance seems particularly broad. Both aromatic (with various substi-
tution patterns) and aliphatic aldehydes were well suited to this
transformation. Good chemical yields and moderate to good
enantioselectivities were obtained uniformly, regardless of elec-
tronics and substitution pattern. Catalysts 4a and 4d consistently
afforded the opposite stereoselectivities with all of the substrates
tested. Typically, catalyst 4a afforded the (S)-enantiomers while
the corresponding (R)-enantiomers of the products were obtained
by using catalyst 4d. This observation might open up the pathway
to enantioselectively prepare both enantiomers of this type of
compounds only using natural amino acid derivatives. The elec-
tronic nature of the substituents only had a minor effect on this
transformation (Table 5, entries 1–11). For both catalysts, rela-
tively high enantiomeric excesses were observed for the aromatic
aldehyde bearing a hydroxyl group in the ortho-position, which
might be involved in hydrogen-bonding with the catalyst (entry
2, 69%, ꢀ74%). The aliphatic aldehyde provided the corresponding
adduct with slightly lower enantioselectivity (Table 5, entry 9)
than the aromatic aldehydes. The heteroaromatic aldehyde pyridi-
nyl-2-carbaldehyde also gave the corresponding products with 63%
and ꢀ67% ee, respectively (Table 5, entry 10).
The pathway of this transformation is proposed in Scheme 1.
Presumably, an unstable imine is formed via a dehydration
Table 5
Asymmetric one-pot synthesis of 2-aryl-2,3-dihydro-4-quinolones catalyzed by 4a or 4d with various substituted aldehydesa
O
O
O
O
20 mol% catalyst
+
+
NH2
R
MeOH, -20oC
N
H
R
N
H
R
5a-5k
6a-6k
6a'-6k'
1
Entry
Aldehyde
R
Product 6
Catalyst 4a
Catalyst 4d
Yieldb (%)
eec,d (%)
Yieldb (%)
eec,d (%)
1
2
3
4
5
6
7
8
C6H5ꢀ
6a
6b
6c
6d
6e
6f
6g
6h
6i
82
85
90
80
88
78
92
80
69
86
88
65
69
67
61
63
59
68
60
59
63
66
72
77
79
65
80
66
80
67
58
75
78
ꢀ70
ꢀ74
ꢀ69
ꢀ63
ꢀ66
ꢀ64
ꢀ72
ꢀ62
ꢀ60
ꢀ67
ꢀ68
o-OHC6H4ꢀ
p-OHC6H4ꢀ
p-BrC6H4ꢀ
m-OCH3C6H4ꢀ
m-ClC6H4ꢀ
p-NMe2C6H4ꢀ
p-NO2C6H4ꢀ
(CH3)2CH2CHꢀ
2-Pyridinylꢀ
3-Indolylꢀ
9
10
11
6j
6k
a
Reaction conditions: 2-aminoacetophenone 1 (1.0 mmol), aldehyde 6a–6k (1.5 mmol), catalyst (4a or 4d, 0.2 mmol), solvent (MeOH, 1 mL), reaction temperature
(ꢀ20 °C), and reaction time (24 h).
b
Yield of the isolated product after chromatography.
c
Determined by chiral HPLC analysis (Chiralcel OD-H column).
d
Absolute configurations were assigned by comparison of the specific rotations and chiral chromatography with the literature data.22a–d

H. Zheng et al. / Tetrahedron: Asymmetry 24 (2013) 875–882
879
O
O
CHO
O
O
catalyst
Ph
+
+
NH2
N
N
H
Ph
N
H
Ph
(E)-1-(2-(benzylideneamino)phenyl)ethanone(imine)
Scheme 1.
R1
SO2
N
H
O
N
HN
O
O
HN
N
H
HN
SO2
SO2
N
N
N
Ph
Ph
H
H
Ph
H
R1
si-face attack
si-face attack
re-face attack
favored
III
R1
unfavored
I
II
Figure 1. Proposed transition state models for the intramolecular Mannich reaction catalyzed by amino acid-derived sulfonamides.
reaction at first. Then, the amino acid-derived sulfonamides cata-
lyze the intramolecular Mannich reaction to provide 2-phenyl-
2,3-dihydroquinolin-4(1H)-ones. In order to account for the stereo-
chemical outcome, several plausible transition state models are
proposed and shown in Figure 1. The transition state model I,
which is attributed to the reaction catalyzed by proline-derived
sulfonamides 4a–c, is similar to the one-proline enamine mecha-
nism proposed by List and Houk.24 Here the carbonyl group of
the imine is activated to form an enamine by the N–H of the pyr-
rolidine moiety, while the C@N of the imine is also activated by
the forming hydrogen-bond between the nitrogen-atom and the
sulfonamide N–H. The enamine attacks the carbon atom of the
C@N on one face and leads to the formation of the favored (S)-
enantiomer as the major product. However, the (R)-enantiomer is
favored as the major product when using primary amine sulfona-
mides 4d–i to catalyze the aforementioned reaction. Two plausible
transition state models II and III are proposed to elaborate upon
this stereoselectivity. As shown in transition state model II (si-face
attack), a severe steric repulsion is involved from the interaction
between sulfonamide unit and the enamine part. However, this
steric effect could be relieved by simply rotating the sulfonamide
unit away from the enamine in the transition state model III (re-
face attack), leading to formation of the corresponding (R)-
enantiomer.
acid derivatives. Moreover, this protocol may find wide applica-
tions in the synthesis of other bioactive nitrogen containing cyclic
structures in future research.
4. Experimental
4.1. General
All reagents were used without purification as commercially
available. The reactions were monitored by TLC (thin layer chroma-
tography). Purification of the reaction products was carried out by
flash chromatography on silica gel (200–300 mesh). Chemical
yields refer to pure isolated substances. Melting points were mea-
sured on a XR-4 apparatus (thermometer uncorrected). Optical
rotations were recorded with a Jasco-P-2000 digital polarimeter.
Nuclear Magnetic Resonance (NMR) spectra were measured using
a Bruker Avance 400 spectrometer operating at 100 MHz for1H
NMR and 100 MHz. Chemical shift values (d) are reported in ppm
relative to either TMS at 0.0 ppm or the NMR solvent peak. NMR
data are reported as follows: chemical shift, multiplicity (s = sin-
glet, d = doublet, t = triplet, q = quartet, m = multiplet, br = broad).
Infrared spectra were recorded on a Nicolet NEXUS 670 FT-IR
spectrophotometer using KBr disks in the 400–4000 cmꢀ1 region.
Enantiomeric excesses were determined by HPLC using Chiralcel
OD-H (Daicel Chemical Industries) column using n-Hexane/i-PrOH
as a mobile phase and detected by UV at 365 nm. The absolute con-
figurations of products 3a and 6a–k were assigned by comparison
of the sign of optical rotation with literature data.22a–d Compounds
4b and 4c (Hua Cat) were prepared according to the reported
procedures.25,26
3. Conclusion
In conclusion, an efficient organocatalytic approach for the
asymmetric preparation of biologically important 2-aryl-2,3-dihy-
dro-quinolin-4(1H)-ones has been developed by utilizing the read-
ily prepared amino acid-derived sulfonamides. Good yields (up to
92%) and moderate to good enantiomeric excesses (up to 74%)
were achieved. The primary and secondary amine sulfonamides
provided the opposite enantioselective outcomes respectively,
which may facilitate the preparation of both enantiomers for 2-
aryl-2,3-dihydro-quinolin-4(1H)-ones using only natural amino
4.2. General method for the synthesis of catalysts 4a–4f
Under a dry nitrogen atmosphere, to a stirred solution of substi-
tuted benzenesulfonamide (10.0 mmol) in dichloromethane
(40 mL) were added Boc-amino acid (11.0 mmol), DMAP (1.21 g,

880
H. Zheng et al. / Tetrahedron: Asymmetry 24 (2013) 875–882
11.0 mmol), and EDCI (2.12 g, 11.0 mmol). The resulting mixture
was stirred at room temperature for 72 h before being partitioned
between EtOAc (150 mL) and aq. HCl (1 M, 100 mL). The organic
layer was washed with half-saturated brine (2 ꢁ 40 mL). The dried
(Na2SO4) extract was concentrated in vacuo and the crude product
was used for the next step without further purification. The depro-
tection of Boc-protected sulfonamides was carried out according to
the general method.27 A solution of crude Boc-protected sulfona-
mides in dichloromethane (20 mL) was cooled to 0 °C. Trifluoro-
acetic acid (5 mL) was added dropwise to this chilled solution
and the reaction mixture was stirred at room temperature for
2 h. Next, the solvent and excess TFA were removed in vacuo.
The residue was redissolved in dichloromethane (10 mL), neutral-
ized with 28% ammonia and the aqueous layer extracted with
dichloromethane (5 ꢁ 15 mL). The combined extracts were washed
with saturated NaCl aqueous solution, dried over Na2SO4, filtered,
and concentrated in vacuo. Next, the resulting mixture was puri-
fied via flash chromatography (CH2Cl2/MeOH = 19:1) to provide
the corresponding sulfonamides 4a–4i.23
(m, 2H), 2.58 (s, 6H), 2.29 (s, 3H); 13C NMR (100 MHz, DMSO-d6)
d 173.6, 140.5, 138.6, 138.4, 136.6, 131.0, 130.2, 128.2, 127.1,
56.6, 37.8, 23.3, 21.4.
4.3.6. N-2,4,6-Tris-(isopropylbenzene)sulfonyl-L-phenylalanine
amide 4h
Light yellow powder, yield: 2.03 g, 43%; ½a D25
¼ ꢀ46:2 (c 1,
ꢂ
MeOH); mp: 150–152 °C; IR (KBr disk)
v
: 3426, 2959, 2868,
1H
1740, 1601, 1496, 1362, 1239, 1060, 977, 880, 672, 566 cmꢀ1
;
NMR (400 MHz, CDCl3) d 7.05–7.30 (m, 7H), 4.33 (t, J = 4.8 Hz,
1H), 3.43 (d, J = 4.0 Hz, 1H), 2.85–2.92 (m, 2H), 2.39–2.41 (m,
1H), 1.15–1.26 (m, 18H); 13C NMR (100 MHz, DMSO-d6) d 172.1,
149.5, 149.2, 139.9, 137.1, 129.9, 128.9, 127.1, 122.6, 56.5, 37.9,
33.8, 28.6, 25.3, 25.1, 24.2.
4.3.7. N-4-Dodecylbenzenesulfonyl-L-phenylalanine amide 4i
White powder, yield: 2.60 g, 50%; ½a D25
¼ ꢀ98:2 (c 1, MeOH);
ꢂ
mp: 206–207 °C; IR (KBr disk)
v
: 3085, 2956, 2926, 1658, 1622,
1H NMR (400 MHz,
1494, 1294, 1137, 979, 898, 699, 585 cmꢀ1
;
CDCl3) d 7.83–7.89 (m, 4H), 6.93–6.99 (m, 5H), 4.58 (br s, 1H),
3.22 (d, J = 3.0 Hz, 2H), 2.58–2.63 (m, 1H); 0.79–1.63 (m, 25H);
13C NMR (100 MHz, DMSO-d6) d 170.1, 135.3, 130.0, 128.7, 127.9,
127.7, 127.2, 55.3, 45.5, 45.2, 36.8, 36.3, 31.7, 29.7, 29.4, 29.1,
27.5, 27.1, 22.6, 22.4, 14.4, 14.3, 12.4.
4.3. Characterization of sulfonamides 4a, 4d–4i
4.3.1. N-2,4,6-Tris-(methylbenzene)sulfonyl-
L
-proline amide 4a
White solid, yield: 1.56 g, 48%; ½a D25
ꢂ
¼ þ67:7 (c 1, CHCl3); mp:
130–132 °C; IR (KBr disk) v: 3495, 2979, 2774, 1603, 1454, 1381,
1264, 1126, 935, 822, 658 cmꢀ1
;
1H NMR (100 MHz, CDCl3) d
4.4. General procedure for the synthesis of 2,3-dihydro-4-quinolone
derivatives and characterization for compounds 6a–6k
6.88 (s, 2H), 4.35 (t, J = 7.4 Hz, 1H), 3.31–3.37 (m, 2H), 2.66 (s,
6H), 2.30–2.40 (m, 2H), 2.26 (s, 3H), 1.92–2.01 (m, 2H), 1.82–1.84
(m, 1H); 13C NMR (100 MHz, CDCl3) d 173.8, 141.2, 138.8, 137.7,
61.6, 46.3, 30.1, 24.8, 22.7, 21.1.
To a stirred solution of 2-aminoacetophenone 1 (135 mg,
1.0 mmol) and aldehydes 5 (1.5 mmol) in MeOH (1 mL), catalyst
4a or 4d (0.2 mmol) was added at ꢀ20 °C. The reaction mixture
was stirred at the same temperature for the required time. After
the 2-aminoacetophenone was consumed as determined by TLC
analysis, the mixture was treated with saturated ammonium chlo-
ride solution (5 mL) and extracted with dichloromethane
(3 ꢁ 10 mL). The combined organic layer was dried over anhydrous
MgSO4, filtered, and concentrated in vacuo. The crude product was
purified via silica gel column chromatography (ethyl acetate/petro-
leum ether = 1:5) to give compounds 6a–6k.22e
4.3.2. N-2,4,6-Tris-(methylbenzene)sulfonyl-
L
-alanine amide 4d
White powder, yield: 1.54 g, 52%; ½a D25
ꢂ
¼ ꢀ34:5 (c 1, MeOH);
mp: 222–223 °C; IR (KBr disk)
v
: 3155, 3102, 2932, 1630, 1568,
1H NMR (100 MHz,
1397, 1280, 1056, 969, 878, 680, 588 cmꢀ1
;
CDCl3) d 7.71 (br s, 1H), 6.78 (s, 2H), 3.37–3.45 (m, 3H), 2.58 (s,
6H), 2.18 (s, 3H), 1.25 (d, J = 4.0 Hz, 3H); 13C NMR (100 MHz,
DMSO-d6) d 173.6, 140.3, 138.7, 138.4, 130.6, 79.6, 50.9, 23.0,
20.7, 17.7.
4.3.3. N-2,4,6-Tris-(isopropylbenzene)sulfonyl-
L
-alanine amide
4.4.1. 2-Phenyl-2,3-dihydroquinolin-4(1H)-one 6a
4e
Pale yellow solid, mp: 150–151 °C (lit.22d mp: 149–150 °C);
White powder, yield: 1.64 g, 42%; ½a D25
ꢂ
¼ ꢀ25:2 (c 1, MeOH);
Catalyzed by 4a: 183 mg, 82% yield; 65% ee, ½a D25
¼ þ17:9 (c 0.5,
ꢂ
mp: 207–210 °C; IR (KBr disk)
v
: 3181, 2956, 2868, 1704, 1596,
1H NMR (400 MHz,
CHCl3); Catalyzed by 4d: 161 mg, 72% yield; ꢀ70% ee;
1397, 1364, 1137, 967, 878, 684, 567 cmꢀ1
;
½
a 2D5
ꢂ
¼ ꢀ19:4 (c 0.5, CHCl3); HPLC analysis: Diacel Chiralcel OD-
DMSO-d6) d 7.00 (s, 2H), 4.61 (t, J = 4.0 Hz, 2H), 3.37–338 (m,
1H), 2.80–2.83 (m, 2H), 1.86–1.87 (m, 3H), 1.28 (d, J = 4.0 Hz,
3H), 1.13 (br s, 18H); 13C NMR (100 MHz, DMSO-d6) d 173.8,
149.5, 140.3, 123.4, 51.7, 39.4, 28.4, 26.5, 24.2, 23.7,17.8.
H, n-Hexane/i-PrOH = 70/30, flow rate = 1 mL/min, k = 365 nm,
Catalyzed by 4a: retention time: 8.2 min (major) and 9.9 min
(minor); Catalyzed by 4d: retention time: 8.4 min (minor) and
10.1 min (major); IR (KBr disk) v: 3324, 3079, 1641, 1607, 1505,
1397, 1252, 1121, 740 cmꢀ1:1H NMR (400 MHz, CDCl3) d 7.87–
7.90 (m, 1H), 7.46–7.49, (m, 2H), 7.33–7.43 (m, 4H), 6.78–6.82
(m, 1H), 6.70–6.73 (m, 1H), 4.75–4.79 (m, 1H), 4.50 (br s, 1H),
2.81–2.90 (m, 2H); 13C NMR (100 MHz, CDCl3) d 192.8, 151.3,
140.7, 135.0, 128.7, 128.2, 127.2, 126.3, 118.6, 117.8, 115.4,
57.8, 45.8.
4.3.4. N-4-Dodecylbenzenesulfonyl-
L
-alanine amide 4f
White solid, yield: 2.35 g, 54%; ½a D25
ꢂ ¼ ꢀ77:4 (c 1, CHCl3); mp:
198–200 °C; IR (KBr disk) v: 3498, 3098, 2946, 2846, 1627, 1587,
1468, 1367, 1280, 1135, 869, 672, 587 cmꢀ1 1H NMR (100 MHz,
;
CDCl3) d 7.56–7.67 (m, 2H), 7.17–7.20 (m, 2H), 3.76–3.81 (m,
1H), 0.68–1.91 (m, 30H); 13C NMR (100 MHz, DMSO-d6) d 173.4,
140.6, 136.5, 128.8, 127.4, 55.7, 45.6, 45.1, 36.9, 36.1, 31.8, 29.8,
29.5, 29.2, 27.6, 27.3, 22.7, 22.4, 14.6, 14.3, 12.3.
4.4.2. 2-(2-Hydroxyphenyl)-2,3-dihydroquinolin-4(1H)-one 6b
Yellow solid, mp: 165–167 °C (lit.22d mp: 164–168 °C); Cata-
lyzed by 4a: 203 mg, 85% yield; 69% ee, ½a D25
¼ þ29:6 (c 0.5, CHCl3);
ꢂ
4.3.5. N-2,4,6-Tris-(methylbenzene)sulfonyl-L-phenylalanine amide
Catalyzed by 4d: 184 mg, 77% yield; ꢀ74% ee, ½a D25
¼ ꢀ31:8 (c 0.5,
ꢂ
4g
CHCl3); HPLC analysis: Diacel Chiralcel OD-H, n-Hexane/i-
PrOH = 70/30, flow rate = 1 mL/min, k = 365 nm, Catalyzed by 4a:
retention time: 5.3 min (major) and 8.5 min (minor); Catalyzed
by 4d: retention time: 5.4 min (minor) and 8.8 min (major); IR
Light yellow powder, yield: 1.86 g, 49%; ½a D25
¼ ꢀ64:4 (c 1,
ꢂ
MeOH); mp: 230–232 °C; IR (KBr disk)
v
: 3461, 3029, 2924,
1629, 1603, 1491, 1359, 1227, 1057, 957, 826, 698, 588 cmꢀ1
;
1H
NMR (400 MHz, CDCl3) d 7.08–7.15 (m, 3H), 7.01 (d, J = 12.0 Hz,
2H), 6.91 (s, 2H), 4.09 (br s, 1H), 3.20–3.24 (m, 2H), 2.99–3.05
(KBr disk)
v:
3539, 3310, 1606, 1538, 1389, 1243, 1095,
768 cmꢀ1
;
1H NMR (400 MHz, CDCl3) d 7.93–7.95 (m, 1H), 7.76

H. Zheng et al. / Tetrahedron: Asymmetry 24 (2013) 875–882
881
(s, 1H), 7.40–7.44 (m, 1H), 7.16–7.24 (m, 1H), 6.90–6.95 (m, 1H),
6.83–6.88 (m, 4H), 4.87–4.92 (m, 1H), 4.72 (s, 1H), 3.06–3.13 (m,
1H), 2.82–2.86 (m, 1H); 13C NMR (100 MHz, CDCl3) d 193.6,
155.3, 150.6, 135.5, 129.9, 128.0, 127.8, 124.8, 120.7, 120.6,
120.5, 117.4, 117.3, 57.6, 43.6.
2.86 (m,1H); 13C NMR (100 MHz, CDCl3) d 192.5, 151.4, 143.1,
135.5, 134.8, 130.1, 128.6, 127.4, 126.7, 124.6, 119.0, 118.7,
116.0, 57.8, 46.2.
4.4.7. 2-(4-(Dimethylamino)phenyl)-2,3-dihydroquinolin-4(1H)-
one 6g
4.4.3. 2-(4-Hydroxyphenyl)-2,3-dihydroquinolin-4(1H)-one 6c
Pale yellow solid, mp: 156–159 °C (lit.22d mp: 158–161 °C); Cat-
Yellow solid, mp: 182–185 °C (lit.22d mp: 182–184 °C); Cata-
lyzed by 4a: 245 mg, 92% yield; 68% ee, ½a D25
¼ þ18:2 (c 0.5, CHCl3);
ꢂ
alyzed by 4a: 215 mg, 90% yield; 67% ee, ½a D25
ꢂ
¼ þ22:4 (c 0.5,
Catalyzed by 4d: 213 mg, 80% yield; ꢀ72% ee, ½a D25
¼ ꢀ19:3 (c 0.5,
ꢂ
CHCl3); Catalyzed by 4d: 189 mg, 79% yield; ꢀ69% ee,
CHCl3); HPLC analysis: Diacel Chiralcel OD-H, n-Hexane/i-
PrOH = 70/30, flow rate = 1 mL/min, k = 365 nm, Catalyzed by 4a:
retention time: 10.4 min (major) and 14.3 min (minor); Catalyzed
by 4d: retention time: 10.2 min (minor) and 14.0 min (major); IR
½
a 2D5
ꢂ
¼ ꢀ23:1 (c 0.5, CHCl3); HPLC analysis: Diacel Chiralcel OD-H,
n-Hexane/i-PrOH = 70/30, flow rate = 1 mL/min, k = 365 nm, Cata-
lyzed by 4a: retention time: 10.5 min (major) and 16.0 min (min-
or); Catalyzed by 4d: retention time: 10.4 min (minor) and
(KBr disk)
v
: 3357, 2898, 1649, 1478, 1328, 1198, 1056, 890,
15.7 min (major); IR (KBr disk)
v
: 3548, 3067, 1653, 1527, 1498,
;
756 cmꢀ1
;
1H NMR (400 MHz, CDCl3) d 7.96–7.98 (m, 1H), 7.24–
1267, 1103, 957, 898, 768 cmꢀ1
1H NMR (400 MHz, CDCl3) d
7.27 (m, 1H), 7.18 (d, J = 8.4 Hz, 2H), 6.77–6.80 (m, 2H), 6.59–
6.62 (m, 2H), 5.79 (br s, 1H), 5.16 (dd, J = 9.6, 3.9 Hz, 1H), 3.53 (s,
6H), 3.02–3.05 (m, 1H), 2.82 (dd, J = 15.4, 3.4 Hz, 1H); 13C NMR
(100 MHz, CDCl3) d 193.9, 151.8, 150.6, 135.3, 128.4, 127.5,
127.2, 118.8, 118.1, 115.9, 112.4, 57.9, 46.3, 40.5.
7.94–7.96 (m, 1H), 7.22–7.26 (m, 3H), 6.77–6.80 (m, 4H), 5.16–
5.21 (m, 1H), 4.64 (br s, 2H), 3.03 (dd, J = 15.4, 5.6 Hz, 1H), 2.81–
2.84 (m, 1H); 13C NMR (100 MHz, CDCl3) d 192.4, 156.5, 149.6,
135.6, 131.0, 127.9, 127.1, 123.3, 117.9, 117.1, 116.1, 55.5, 42.6.
4.4.4. 2-(4-Bromophenyl)-2,3-dihydroquinolin-4(1H)-one 6d
Yellow solid, mp: 160–162 °C (lit.28 mp: 160 °C); Catalyzed by
4.4.8. 2-(4-Nitrophenyl)-2,3-dihydroquinolin-4(1H)-one 6h
Orange solid, mp: 201–202 °C (lit.22d mp: 200–202 °C); Cata-
4a: 241 mg, 80% yield; 61% ee, ½a D25
ꢂ
¼ þ16:8 (c 0.5, CHCl3); Cata-
lyzed by 4a: 214 mg, 80% yield; 60% ee, ½a D25
¼ þ17:9 (c 0.5, CHCl3);
ꢂ
lyzed by 4d: 196 mg, 65% yield; ꢀ63% ee, ½a D25
ꢂ
¼ ꢀ17:4 (c 0.5,
Catalyzed by 4d: 180 mg, 67% yield; ꢀ62% ee,½a D25
¼ ꢀ19:4 (c 0.5,
ꢂ
CHCl3); HPLC analysis: Diacel Chiralcel OD-H, n-Hexane/i-
PrOH = 70/30, flow rate = 1 mL/min, k = 365 nm, Catalyzed by 4a:
retention time: 8.8 min (major) and 17.9 min (minor); Catalyzed
by 4d: retention time: 8.9 min (minor) and 18.0 min (major); IR
CHCl3); HPLC analysis: Diacel Chiralcel OD-H, n-Hexane/i-
PrOH = 70/30, flow rate = 1 mL/min, k = 365 nm, Catalyzed by 4a:
retention time: 13.6 min (major) and 18.5 min (minor); Catalyzed
by 4d: retention time: 13.5 min (minor) and 18.4 min (major); IR
(KBr disk)
v
: 3343, 2901, 1623, 1345, 1112, 1023, 821, 713 cmꢀ1
;
(KBr disk)
v
: 3358, 2910, 1670, 1467, 1368, 1188, 1073, 868,
1H NMR (400 MHz, CDCl3) d 7.86 (dd, J = 7.8, 1.6 Hz, 1H), 7.47–
7.54 (m, 2H), 7.27–7.36 (m, 3H), 6.76–6.78 (m, 1H), 6.66 (d,
J = 8.6 Hz, 1H), 4.72 (dd, J = 12.7, 4.7 Hz, 1H), 4.43 (br s, 1H),
2.79–2.85 (m, 2H); 13C NMR (100 MHz, CDCl3): d 192.8, 151.4,
140.2, 135.4, 132.6, 128.3, 127.6, 122.3, 119.1, 118.7, 116.5, 57.8,
46.5.
762 cmꢀ1
;
1H NMR (400 MHz, CDCl3) d 8.16–8.19 (m, 2H), 7.94–
7.97 (m, 1H), 7.82–7.85 (m, 2H), 7.24–7.27 (m, 1H), 6.79–6.82
(m, 2H), 5.80 (br s, 1H), 5.22–5.24 (m, 1H), 2.97 (dd, J = 15.6,
3.6 Hz, 1H), 2.79 (dd, J = 15.6, 5.4 Hz, 1H); 13C NMR (100 MHz,
CDCl3) d 190.6, 151.3, 141.5, 139.7, 134.8, 128.6, 124.3, 123.8,
118.6, 117.4, 115.8, 57.3, 47.1.
4.4.5. 2-(3-Methoxyphenyl)-2,3-dihydroquinolin-4(1H)-one 6e
Brownish yellow solid, mp: 128–130 °C (lit.22d mp: 129–
131 °C); Catalyzed by 4a: 223 mg, 88% yield; 63% ee,
4.4.9. 2-Isobutyl-2,3-dihydroquinolin-4(1H)-one 6i
Brownish yellow sticky oil; Catalyzed by 4a: 140 mg, 69% yield;
59% ee, ½a 2D5
¼ þ24:8 (c 0.5, CHCl3); Catalyzed by 4d: 118 mg, 58%
ꢂ
½
a 2D5
ꢂ
¼ þ22:1 (c 0.5, CHCl3); Catalyzed by 4d: 202 mg, 80% yield;
yield; ꢀ60% ee, ½a D25
¼ ꢀ25:2 (c 0.5, CHCl3); HPLC analysis: Diacel
ꢂ
ꢀ66% ee, ½a 2D5
ꢂ
¼ ꢀ23:2 (c 0.5, CHCl3); HPLC analysis: Diacel Chiral-
Chiralcel OD-H, n-Hexane/i-PrOH = 70/30, flow rate = 1 mL/min,
k = 365 nm, Catalyzed by 4a: retention time: 9.7 min (major) and
11.5 min (minor); Catalyzed by 4d: retention time: 9.5 min (min-
cel OD-H, n-Hexane/i-PrOH = 70/30, flow rate = 1 mL/min,
k = 365 nm, Catalyzed by 4a: retention time: 9.2 min (major) and
11.8 min (minor); Catalyzed by 4d: retention time: 9.4 min (min-
or) and 11.1 min (major); IR (neat)
v: 3360, 2945, 1664, 1345,
or) and 12.0 min (major); IR(KBr disk)
v
: 3348, 2923, 1659, 1375,
1278, 1130, 898, 749 cmꢀ1 1H NMR (400 MHz, CDCl3) d 7.92–
;
1234, 1191, 1073, 847 cmꢀ1 1H NMR (400 MHz, CDCl3) d 7.95–
;
7.94 (m, 1H), 7.24–7.27 (m, 1H), 6.75–6.81 (m, 2H), 5.48 (br s,
1H), 3.96–4.04 (m, 1H), 2.23–2.28 (m, 1H), 2.11–2.18 (m, 1H),
1.36–1.56 (m, 3H), 0.88 (s, 6H); 13C NMR (100 MHz, CDCl3) d
192.5, 150.8, 131.6, 127.2, 121.9, 116.8, 116.4, 46.5, 43.9, 43.1,
24.9, 22.2.
7.97 (m, 1H), 7.21–7.28 (m, 2H), 6.98–7.05 (m, 2H), 6.77–6.82
(m, 3H), 5.71 (br s, 1H), 5.14–5.17 (m, 1H), 3.76 (s, 3H), 2.95–
3.06 (m, 1H), 2.73–2.84 (m, 1H); 13C NMR (100 MHz, CDCl3) d
191.5, 159.7, 149.6, 143.6, 130.8, 129.4, 127.0, 123.2, 121.3,
117.8, 116.7, 114.4, 112.8, 55.9, 55.6,42.3.
4.4.10. 2-(Pyridin-2-yl)-2,3-dihydroquinolin-4(1H)-one 6j
Brownish yellow solid, mp: 127–129 °C (lit.22d mp: 128–
130 °C); Catalyzed by 4a: 193 mg, 86% yield; 63% ee,
4.4.6. 2-(3-Chlorophenyl)-2,3-dihydroquinolin-4(1H)-one 6f
Pale yellow solid, mp: 144–146 °C (lit.22dmp: 143–145 °C); Cat-
alyzed by 4a: 200 mg, 78% yield; 59% ee, ½a D25
ꢂ
¼ þ14:2 (c 0.5,
½
a 2D5
ꢂ
¼ þ18:4 (c 0.5, CHCl3); Catalyzed by 4d: 168 mg, 75% yield;
CHCl3); Catalyzed by 4d: 170 mg, 66% yield; ꢀ64% ee,
ꢀ67% ee, ½a 2D5
¼ ꢀ19:6 (c 0.5, CHCl3); HPLC analysis: Diacel Chiral-
ꢂ
½
a 2D5
ꢂ
¼ ꢀ15:4 (c 0.5, CHCl3); HPLC analysis: Diacel Chiralcel OD-H,
cel OD-H, n-Hexane/i-PrOH = 70/30, flow rate = 1 mL/min, k=
365 nm, Catalyzed by 4a: retention time: 7.8 min (major) and
11.2 min (minor); Catalyzed by 4d: retention time: 7.6 min (min-
n-Hexane/i-PrOH = 70/30, flow rate = 1 mL/min, k= 365 nm, Cata-
lyzed by 4a: retention time: 11.3 min (major) and 15.6 min (min-
or); Catalyzed by 4d: retention time: 11.2 min (minor) and
or) and 11.0 min (major); IR (KBr disk)
v
: 3365, 2952, 1668,
;
15.7 min (major); IR(KBr disk)
v
: 3314, 2919, 1656, 1608, 1438,
1607, 1323, 1247, 1154, 1067, 983, 750 cmꢀ1
1H NMR (400 MHz,
1284, 1105, 758 cmꢀ1 1H NMR (400 MHz, CDCl3) d 7.93–7.96 (m,
;
CDCl3) d 8.58 (d, J = 7.8 Hz, 1H), 7.86–7.88 (m, 1H), 7.63 (m, 1H),
7.15–7.34 (m, 3H), 6.77–6.87 (m, 2H), 5.15 (dd, J = 9.0, 3.4 Hz,
1H), 4.48 (br s, 1H), 3.13–3.16 (m, 1H), 2.77 (dd, J = 15.6, 3.9 Hz,
1H), 7.48 (s, 1H), 7.25–7.32 (m, 4H), 6.78–6.80 (m, 2H), 5.76 (br
s, 1H), 5.14–5.20 (m, 1H), 3.04 (dd, J = 15.0, 3.3 Hz, 1H), 2.84–

882
H. Zheng et al. / Tetrahedron: Asymmetry 24 (2013) 875–882
1H); 13C NMR (100 MHz, CDCl3) d 191.7, 153.5, 150.1, 140.9, 136.7,
134.5, 131.4, 126.8, 125.0, 124.1, 117.1, 115.7, 52.1, 46.3.
4. Friestad, G. K.; Mathies, A. K. Tetrahedron 2007, 63, 2541–2569.
5. Charette, A. B.; Boezio, A. A.; Cote, A.; Moreau, E.; Pytkowicz, J.; Desrosiers, J. N.;
Legault, C. Pure Appl. Chem. 2005, 77, 1259–1267.
6. List, B. J. Am. Chem. Soc. 2000, 122, 9336–9337.
7. List, B.; Pojarliev, P.; Biller, W. T.; Martin, H. J. J. Am. Chem. Soc. 2002, 124, 827–
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8. Tanaka, F.; Barbas, C. F. In Aldol and Mannich-Type Reactions; Dalko, P., Ed.;
Wiley-VCH: Weinheim, 2007; pp 19–55.
9. Verkade, J. M. M.; Hemert, L. J. C. V.; Quaedflieg, P. J. L. M.; Rutjes, F. P. J. T. Chem.
Soc. Rev. 2008, 37, 29–41.
10. Kobayashi, S.; Mori, Y.; Fossey, J. S.; Salter, M. M. Chem. Rev. 2011, 111, 2626–
2704.
4.4.11. 2-(4-(1H-Indol-3-yl)phenyl)-2,3-dihydroquinolin-4(1H)-
one 6k
Yellow solid, mp: 170–172 °C (lit.28 mp: 172 °C); Catalyzed by
4a: 231 mg, 88% yield; 66% ee,½a D25
¼ þ10:9 (c 0.5, CHCl3); Cata-
ꢂ
lyzed by 4d: 204 mg, 78% yield; -68% ee, ½a D25
¼ ꢀ11:2 (c 0.5,
ꢂ
CHCl3); HPLC analysis: Diacel Chiralcel OD-H, n-Hexane/i-
PrOH = 70/30, flow rate = 1 mL/min, k = 365 nm, Catalyzed by 4a:
retention time: 8.8 min (major) and 18.0 min (minor); Catalyzed
by 4d: retention time: 8.5 min (minor) and 17.6 min (major); IR
11. Mukherjee, S.; Yang, J. W.; Hoffmann, S.; List, B. Chem. Rev. 2007, 107, 5471–
5569.
12. Xu, L.-W.; Lu, Y.-X. Org. Biomol. Chem. 2008, 6, 2047–2053.
13. Davie, E. A. C.; Miler, S. J. Chem. Rev. 2007, 107, 5759–5812.
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15. Enders, D.; Grondal, C. Angew. Chem., Int. Ed. 2005, 44, 1210–1212.
16. Yang, H.; Carter, R. G. J. Org. Chem. 2009, 74, 2246–2249.
17. Uraguchi, D.; Terada, M. J. Am. Chem. Soc. 2004, 126, 5356–5357.
18. Lou, S.; Taoka, B. M.; Ting, A.; Schaus, S. E. J. Am. Chem. Soc. 2005, 127, 11256–
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(KBr disk)
v
:3335, 2922, 1648, 1602, 1328, 1267, 1134, 1027,
;
973, 740 cmꢀ1
1H NMR (400 MHz, CDCl3) d 8.30 (br s, 1H), 7.90–
7.92 (m, 1H), 7.87 (d, J = 8.0 Hz, 1H), 7.31–7.42 (m, 2H), 7.14–
7.25 (m, 3H), 6.76–6.80 (m, 1H), 6.69 (d, J = 8.0 Hz, 1H), 5.08 (dd,
J = 12.6, 3.4 Hz, 1H), 4.66 (br s, 1H), 3.12–3.20 (m, 1H), 2.86–2.91
(m, 1H); 13C NMR (100 MHz, CDCl3) d 194.4, 151.7, 136.4, 135.5,
127.7, 125.5, 122.7, 122.2, 119.9, 119.3, 119.0, 118.3, 115.8,
111.5, 51.1, 45.2.
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We gratefully acknowledge the financial support from the Cen-
tral South University, National Natural Science Foundation of China
(21276282) and Hunan Provincial Science & Technology Depart-
ment (2012WK2007).
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