Dipeptide-catalyzed direct asymmetric aldol reactions in the presence of water

Article abstract of DOI:10.1016/j.tet.2007.05.077

The l-proline-based dipeptide has been discovered and developed as an efficient catalyst for the direct asymmetric aldol reactions of unmodified ketones with various aldehydes including aromatic, aliphatic, heteroaromatic, and unsaturated aldehydes in the presence of water at 0 °C. The resulted methodology and optimal conditions led to the corresponding aldol products with high yields (up to 94%) and good enantioselectivities (up to 97% ee).

Full text of DOI:10.1016/j.tet.2007.05.077

Tetrahedron 63 (2007) 7892–7898
Dipeptide-catalyzed direct asymmetric aldol
reactions in the presence of water
a
Meng Lei, Lanxiang Shi, Gong Li, Shilv Chen, Weihai Fang,
a
a
c
c,*
a
a
Zemei Ge, Tieming Cheng and Runtao Li
a,b,
*
a
School of Pharmaceutical Sciences, Peking University, Beijing 100083, PR China
State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing 100083, PR China
b
c
Department of Chemistry, Beijing Normal University, Beijing 100875, PR China
Received 19 March 2007; revised 20 May 2007; accepted 22 May 2007
Available online 25 May 2007
Abstract—The L-proline-based dipeptide has been discovered and developed as an efficient catalyst for the direct asymmetric aldol reactions
of unmodified ketones with various aldehydes including aromatic, aliphatic, heteroaromatic, and unsaturated aldehydes in the presence of
ꢀ
water at 0 C. The resulted methodology and optimal conditions led to the corresponding aldol products with high yields (up to 94%) and
good enantioselectivities (up to 97% ee).
Ó 2007 Elsevier Ltd. All rights reserved.
1
. Introduction
dipeptide-based organocatalyst that efficiently catalyzed
direct asymmetric aldol reaction in the presence of water
with high yields (up to 94%) and good enantioselectivities
(up to 97% ee).
The aldol reaction is one of the most powerful methods for
the formation of C–C bonds in organic synthesis. In recent
1
years, organocatalytic asymmetric direct aldol reactions
have received great attention, and various organocatalysts
have been developed in order to achieve high diastereomeric
2
. Results and discussion
2
and enantiomeric selectivities. However, these reactions
were typically performed in organic solvents, such as
2
.1. Design and preparation of catalysts
3
DMSO, DMF, or chloroform. Although addition of a small
amount of water often accelerates reactions and/or improves
We have previously reported that a combination of Pro–Phe
1) with N-methyl morpholine (NMM) as a base and PEG400
as a surfactant (Pro–Phe/NMM/PEG400) efficiently cata-
(
4
enantioselectivities, large amount of water or aqueous
buffer typically resulted in low yield with low or no enantio-
selectivity. Water as a preferred reaction solvent offers a
11
lyzed the asymmetric aldol reactions in DMSO. Recently,
5
12
13
14
15
16
Gong, Kudo, Tsogoeva, C ꢀo rdova, and Lu also ex-
amined the aldol reactions catalyzed by some amino acids
and small dipeptides in different reactive systems including
series of advantages over organic solvents, such as safety,
convenience, economy, and environmental benign, etc.
Therefore, utilizing water as reaction solvent for the devel-
opment of enantioselective aldol reactions is urgently
needed, especially for the discovery of new small organic
molecule catalysts to catalyze this critical reaction. Re-
organic solvents, organic solvents/H O mixture or aqueous
2
media. Though the catalysts used in these reports were easily
synthesized, there were still no very successful examples
on the use of this kind of catalysts in direct asymmetric aldol
reactions for a broad scope of new substrates and desired re-
sults in water. Inspired by aldolase enzymes and antibodies
catalyzed asymmetric biochemical aldol reactions in water
and based on our previous work, we applied our catalytic
system in the aldol reaction of cyclohexanone (6a) with
-pyridinecarbaldehyde (7a) in the presence of water. It is
6
7
cently, while our research is in progress, Hayashi, Barbas,
8
9
10
Zhao, Pericas, and Gong reported the direct asymmetric
aldol reactions catalyzed by some proline derivatives with
high diastereomeric and enantioselectivities in the presence
of water or in water. Therefore, we are prompted to disclose
our discovery in this important area. Herein, we report a new
17
11
4
interesting to find that the reaction proceeded very smoothly
under emulsion conditions with good yield and enantioselec-
tivity (Table 1, entry 1, 91%, 73% ee). We were encouraged
by this result and four new dipeptides (Fig. 1, 2–5) were de-
signed by replacing the benzyl in Pro–Phe (1) with various
Keywords: Organocatalysis; Asymmetric aldol reaction; Dipeptide; In the
presence of water.
*
Corresponding authors. Tel.: +86 10 58805382 (W.F.); tel.: +86 10
2801504; fax: +86 10 82716956 (R.L.); e-mail addresses: fangwh@
bnu.edu.cn; lirt@mail.bjmu.edu.cn
8
0
040–4020/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2007.05.077

M. Lei et al. / Tetrahedron 63 (2007) 7892–7898
7893
Table 1. Screening of reaction conditions in the direct asymmetric aldol
reaction of cyclohexanone (6a) with 4-pyridinecarbaldehyde (7a) in the
presence of water
4-pyridylaldehyde in the presence of water, and the results
are listed in Table 1.
a
O
CHO
O
OH
It can be seen from Table 1 that all the dipeptides utilized
gave excellent yields (>90%), however, the enantioselectiv-
ities varied (range from 69% to 85% ee). Size of the side
chains in dipeptides significantly influenced the catalytic
efficiency. For example, the catalyst 5 containing the largest
side chain gave the best result with 85% ee and 78:22 dr
Cat. (20mol%)
+
H O, 0 °C
2
N
7a
N
6a
8a
ꢀ
b
Time (h) T ( C) Yield (%) dr anti:syn ee (%)
c
c
Entry Catalyst
(
entry 5), and the catalyst 2 containing the smallest side
1
2
3
4
5
6
7
8
9
Pro–Phe (1) 3.5
Pro–Leu (2) 3.5
0
0
0
0
0
10
20
0
91
90
92
94
92
93
94
88
93
72:28
58:42
67:33
68:32
78:22
69:31
60:40
63:37
76:24
73
69
75
77
85
78
77
75
85
chain showed the lowest catalytic selectivity (entry 2, 69%
ee and 58:42 dr). Raising the temperature slightly acceler-
ated the reaction, but the ee and dr values decreased in
some extent (entries 5–7). Entries 8 and 9 showed the effects
of the ratios of donor 6a to acceptor 7a on the reaction rate
and the selectivity. The decrease of their ratio from 4:1 to 2:1
led to slightly lower yield and selectivity (entry 8), and the
increase of their ratio from 4:1 to 6:1 did not improve the
yield and selectivity (entry 9). Therefore, the ratio of 4:1
was most suitable and adopted for further studies.
Pro–Ile (3)
3
Pro–Tyr (4) 2.5
Pro–Trp (5) 2.5
Pro–Trp (5)
Pro–Trp (5)
Pro–Trp (5)
2
2
6
d
e
Pro–Trp (5) 2.5
0
a
Reaction was performed in a solution of 1 mmol scale of aldehyde and
6
equiv of ketone with 0.2 mmol catalyst, 0.2 mmol NMM, 0.05 mmol
ꢀ
PEG400, and 1.5 mL water at 0 C.
Isolated yield of the corresponding product.
Determined by chiral-phase HPLC.
Donor 6a (2 mmol, 2 equiv) was used.
Donor 6a (4 mmol, 4 equiv) was used.
b
c
d
e
We further investigated the critical roles and effects of bases
and surfactants on the asymmetric aldol reaction. In order to
get more accurate results, 4-nitrobenzaldehyde (7b) was se-
lected as the acceptor to react with 6a in the presence of cat-
alyst 5 due to its lower activity and longer reaction time than
7a. As shown in Table 2, in the absence of both base and sur-
factant, only trace of product was detected by TLC even after
20 h (entry 1). However, when the base NMM or the surfac-
tant polyethylene glycol 400 (PEG400) was used separately
in the reaction, the aldol reaction products were obtained in
yields of 90% and 60%, anti:syn ratios of 87:13 and 97:3, ee
values of 77% and 90%, respectively (entries 2 and 3). Fur-
ther, the yield and enantioselectivity are all excellent in the
presence of both base and surfactant PEG400 (entry 4, yield
of 92% and 92% ee). Therefore, the presence of base and
surfactant is definitely essential for the success of this reac-
tion. According to the phenomenon of the experiment, most
of the catalyst was excluded from the reaction system as
a form of solid in the absence of base (entry 3), and contras-
tively, the emulsion reaction system was formed in the pres-
ence of the base (entry 4), we presumed that the equivalent of
catalyst and base might form the carboxylate of Pro–Trp un-
der the reaction conditions. As a comparison, we also carried
out the reaction in DMSO (entry 5) and obtained the aldol
product in yield of 84% with 85% ee, which are obviously
larger side chains to further improve the diastereo- and enan-
tioselectivities of the aldol reactions. The design of new cat-
alysts was based on the following two principles: (1) keeping
the proline unit and the hydrogen atom connected with the
nitrogen of amide unit in the catalyst is necessary, which
has been demonstrated in our previous work; (2) a small
organic catalyst with appropriate hydrophobic groups should
assemble with hydrophobic reactants in water and sequester
the transition state from water, which was hypothesized and
1
1
8
demonstrated by Barbas.
Dipeptides 1–5 were synthesized from the condensation of
Boc-Pro-OH with the corresponding amino acid methyl es-
ter hydrochlorides, following deprotection with NaOH and
trifluoroacetic acid in sequence according to the general
1
8
method for the preparation of dipeptides.
2.2. Screening of catalysts and optimization
of reaction conditions
The catalytic efficiency of dipeptides 1–5 was examined by
the direct asymmetric aldol reaction of cyclohexanone with
CH2Ph
H
COOH
CH2CH(CH3)CH3
H
COOH
CH(CH )CH CH
3 2 3
O
O
O
H
N
H
N
H
N
H
COOH
N
H
N
H
N
H
Pro-Phe
1
Pro-Leu
2
Pro-Ile
3
H
N
OH
H2C
O
H2C
O
H
H
N
H
COOH
N
H
COOH
N
H
N
H
Pro-Tyr
4
Pro-Trp
5
Figure 1. The structure of dipeptides 1–5.

7894
M. Lei et al. / Tetrahedron 63 (2007) 7892–7898
a
Table 2. Efficiency of different additives for the direct asymmetric intermolecular aldol reaction between 6a and 7a or 7b in the presence of water
O
O
OH
O
Cat.5 (20mol%)
R
+
H
R
H O, 0 °C
2
6a
7a-b
8a: R=4-pyridyl
b: R=4-nitrophenyl
8
b
c
Yield (%)
d
dr anti:syn
d
ee anti (%)
Entry
Product
Base
Surfactant
Time (h)
1
2
3
4
8b
8b
8b
8b
8b
8a
8a
8a
8a
8a
8a
8a
8a
8a
8a
8a
8a
8a
8a
8a
8a
—
NMM
—
NMM
NMM
NMM
DMAP
Pyridine
Triethylamine
N,N-Diisopropyl ethylamine
HMTA
N-Methyl piperidine
Hexamethyl disilylamine
1-Methyl pyrrolidine
DABCO
NMM
DABCO
NMM
DABCO
—
—
20
18
20
16
8
2.5
3
4
Trace
90
60
92
84
93
92
90
93
92
91
92
91
93
93
92
93
92
92
93
92
—
87:13
91:9
—
77
90
92
85
85
79
80
78
79
84
80
81
80
86
81
80
82
82
86
80
PEG400
PEG400
PEG400
PEG400
PEG400
PEG400
PEG400
PEG400
PEG400
PEG400
PEG400
PEG400
PEG400
PGME5000
PGME5000
TBAB
81:19
90:10
76:24
83:17
83:17
80:20
80:20
78:22
85:15
80:20
78:22
77:23
75:25
77:23
50:50
50:50
75:25
82:18
e
5
6
7
8
9
2
1
1
1
1
1
1
1
1
1
1
2
2
0
1
2
3
4
5
6
7
8
9
0
1
2.5
3.5
2.5
2.5
2.5
2.5
2.5
2.5
2.5
2.5
2.5
2.5
TBAB
SDS
SDS
NMM
DABCO
a
Reaction was performed at 1 mmol scale of the aldehyde and 4 equiv of ketone with catalyst 5 (0.2 mmol), base (0.2 mmol), and surfactant (0.05 mmol) in
.5 mL water.
NMM: N-methylmorpholine; DMAP: 4-(dimethylamino)pyridine; HMTA: hexamethylenetetramine; DABCO: 1,4-diazabicyclo[2.2.2]octane; PEG400:
1
b
polyethylene glycol 400; TBAB: tetrabutylammonium bromide; SDS: sodium dodecyl sulfate; PGME5000: propylene glycol methyl ether.
c
d
e
Isolated yield of the corresponding product.
Determined by chiral-phase HPLC.
DMSO as solvent.
lower than that in the presence of water (entry 4). So water is
essential for this reaction.
Based on our extensive screening results, we concluded that
the optimal reaction conditions were to utilize Pro–Trp (5) as
a catalyst, NMM/SDS (A) or DABCO/PEG400 (B) as an ad-
ditive, and H O as solvent at 0 C. In the reaction system, the
ꢀ
Subsequently, the influence of different amines with highly
steric hindrance on the reaction by using catalyst 5
2
base might form the carboxylate with catalyst, which could
increase the solubility in water; the surfactant could increase
the interfacial areas of water and organic reagent. Therefore,
it should be the cooperation of catalyst, base, and surfactant,
which led to the effective catalytic activity of our reaction
system.
(
20 mol %) and PEG400 (5 mol %) was further studied.
The reaction of 7a with 6a was used as a model reaction (en-
tries 6–15). The results showed that all the amines provided
excellent yields (90–93%), whereas the enantioselectivities
were different. Among the screened amines, both NMM
and 1,4-diazabicyclo[2.2.2]octane (DABCO) gave the best
enantioselectivities of 85% ee (entry 6) and 86% ee (entry
2.3. Substrate generality
1
5), respectively.
Under our optimized reaction conditions, the application of
dipeptide 5 in direct asymmetric intermolecular aldol reac-
tion between different acceptors and donors was further ex-
plored. A series of aldehyde acceptors, including aromatic,
aliphatic, heteroaromatic, and unsaturated aldehydes, were
examined. Subsequently, some ketone donors were investi-
gated. The data are summarized in Table 3.
To further optimize the reaction conditions, we then turned
our attention to explore the best surfactant and the combina-
tion of base with surfactant in the presence of NMM or
DABCO (entries 16–21). When tetrabutyl ammonium
bromide (TBAB) was used as a surfactant, good enantio-
selectivity was observed, however, there was no diastereo-
selectivity (entries 18 and 19); combination of DABCO
with sodium dodecyl sulfate (SDS) significantly increased
the diastereoselectivity (anti:syn, 82:18), but the enantio-
selectivity slightly decreased; the combination of NMM
with SDS (entry 20, anti:syn 75:25 and 86% ee) gave the
similar result as DABCO/PEG400 (entry 15, anti:syn
It can easily be seen from Table 3 that all studied aldol reac-
tions catalyzed by Pro–Trp 5 in the presence of water
afforded high yields (up to 94%) and splendid selectivities
(up to 99:1 dr and 97% ee). The most noticeable advan-
tage of our discovery is that the reaction can be applied to
a variety of acceptors and donors. Especially, when 6a was
used as a donor, the reactions with a series of aldehydes, in-
cluding aromatic, aliphatic, heteroaromatic, and unsaturated
7
7:23 and 86% ee). Thus, the combination systems of
NMM/SDS (A) and DABCO/PEG400 (B) were superior to
the others.

M. Lei et al. / Tetrahedron 63 (2007) 7892–7898
7895
a
Table 3. Reactions of aliphatic and cyclic ketones (6a–d) with various aldehydes (7a–l) catalyzed by catalyst 5 in the presence of water
O
OH
O
Cat. 5 (20mol%)
R2
+
R2
RCHO
R
0
°C, H O
2
R1
R1
8a-q
6a-d
7a-l
1
Entry R , R
2
b
Product Additive Time (h) Yield (%) dr anti:syn
c
d
d
ee anti:syn (%)
R
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
–(CH
–(CH
–(CH
–(CH
–(CH
–(CH
–(CH
–(CH
–(CH
–(CH
–(CH
–(CH
–(CH
–(CH
–(CH
–(CH
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
)
)
)
)
)
)
)
)
)
)
)
)
)
)
)
)
4
4
4
4
4
4
4
4
4
4
4
4
4
3
3
3
– (6a)
– (6a)
– (6a)
– (6a)
– (6a)
– (6a)
– (6a)
– (6a)
– (6a)
– (6a)
– (6a)
– (6a)
– (6a)
– (6b)
– (6b)
– (6b)
(6c)
Pyridin-4-yl (7a)
4-Nitrophenyl (7b)
4-Nitrophenyl (7b)
2-Nitrophenyl (7c)
3-Nitrophenyl (7d)
4-Cyanophenyl (7e)
Phenyl (7f)
6-Nitro-1,3-dihydroisobenzofuran-5-yl (7g) 8g
6-Nitro-1,3-dihydroisobenzofuran-5-yl (7g) 8g
4-Methyloxyphenyl (7h)
2-Chlorophenyl (7i)
5-Nitrofuran-2-yl (7j)
Styryl (7k)
8a
8b
8b
8c
8d
8e
8f
B
A
B
B
A
A
B
A
B
A
A
A
A
B
B
B
A
A
A
2.5 93
16 (20) 94 (48)
77:23 86:-
83:17 (90:10) 92:- (70:-)
e
e
e
e
16
26
93
88
89
94
72
70
68
67
73
90
81
82
80
85
94
81
67
90:10
>99:1
90:10
93:7
97:-
89:-
80:-
85:-
88:-
93:-
95:-
83:-
90:-
85:83
72:-
88:40
81:72
79:62
58
20
28
208
230
260
210
160
12
98:2
89:11
>99:1
95:5
0
1
2
3
4
5
6
7
8
9
8h
8i
8j
8k
8l
8m
8n
8o
8p
8q
99:1
53:47
76:24
41:59
40:60
35:65
—
32
8
18
2-Nitrophenyl (7c)
3-Nitrophenyl (7d)
4-Nitrophenyl (7b)
4-Nitrophenyl (7b)
2-Propyl (7l)
8
3
70
H, CH
H, CH
3
3
(6c)
2-Propyl, CH
—
95:5
67
83:-
3
(6d) 4-Nitrophenyl (7b)
180
a
b
c
d
e
ꢀ
Reaction was performed at 1 mmol scale of aldehyde and 4 equiv of ketone in 1.5 mL water at 0 C.
A catalyst/NMM/SDS¼0.2:0.2:0.05 (mmol); B catalyst/DABCO/PEG400¼0.2:0.2:0.05 (mmol).
Isolated yield of the corresponding product.
Determined by chiral-phase HPLC.
The dipeptide Val–Val as the catalyst.
aldehydes, were completed smoothly and excellently (from
entry 1 to 13). It can be concluded from the results that the
aromatic aldehydes with substituents at 2-position generally
gave excellent diastereoselectivities (entries 4, 9, and 11;
anti:synꢁ99:1). In terms of enantioselectivity, the aromatic
aldehydes with electron-withdrawing groups usually
afforded higher enantioselectivity as compared to other alde-
hydes. Such as, 7b and 6-nitro-1,3-dihydroisobenzofuran-5-
carbaldehyde (7g) provided the highest ee values in both A
and B additive systems (entries 2, 3 and entries 8, 9; >92%
aldehydes (from entry 2 to 6 and entry 12) were favorable to
the reaction. Therefore, the reactions typically completed
much faster than those of the aromatic aldehydes with an
electron-donating group on the phenyl rings (entries 9 and
10). When the same acceptor was utilized, 6b and 6c reacted
faster than 6a (compare: entry 4 and entry 14; entry 5 and
entry 15; entry 3 and entry 17; etc.). In contrast, 6d required
longer time to complete the reaction and also gave moderate
yield (entry 19, 180 h, 67%).
1
5
ee). During our studying progress, C ꢀo rdova reported aldol
reaction catalyzed by dipeptide Val–Val in water, so we com-
pared the Val–Val with Pro–Trp in the optimal reaction con-
ditions. The dipeptide Pro–Trp exhibited the better catalytic
activities and the results are shown in Table 3. When 2-
nitrobenzaldehyde (7c) and 3-nitrobenzaldehyde (7d) were
utilized as acceptors, the enantioselectivities reached 89%
ee and 80% ee, respectively. Besides, both heteroaromatic
aldehydes, the 7a and 5-nitrofuran-2-carbaldehyde (7j),
were also good substrates to be used in the aldol reactions
3. Conclusions
We have developed and firstly utilized dipeptide Pro–Trp as
an effective organocatalyst. Extensive studies indicated that
this catalyst efficiently catalyzed the direct asymmetric in-
ꢀ
termolecular aldol reaction in the presence of water at 0 C.
The methodology and reaction conditions can be broadly
utilized to a variety of cyclic or acyclic ketones and various
aldehydes, including aromatic, aliphatic, heteroaromatic,
and unsaturated aldehydes. The favorable additives were
discovered to improve the catalytic effects. And in all cases,
the corresponding catalytic aldol products were obtained in
high yields (up to 94%) and good enantioselectivities (up to
97% ee).
(entry 1, 86% ee; entry 12, 85% ee). Particularly, the cinna-
maldehyde (7k) was used as acceptor with good yield and
moderate enantioselectivity for the first time (entry 13,
8
1% yield and 72% ee). Compared with 6a, cyclopentanone
6b) and 4-methyl-2-pentanone (6d) as donors also afforded
(
good enantioselectivities (entries 14–16 and 19, 79–88% ee).
Moreover, the donor acetone (6c) exhibited moderate enan-
tioselectivities (entry 17, 58% ee; entry 18, 67% ee).
4. Experimental section
4.1. General remarks
Though the catalytic effects in enantioselectivities were
good in most cases, the reaction times were greatly different
(from 2.5 h to 260 h), and the yields of the products varied.
When 6a was selected as the donor, electron-poor aromatic
THF were dried with P O for four days and refluxed over
2
5
˚
diphenylketone and sodium, and then distilled onto 4 A

7896
M. Lei et al. / Tetrahedron 63 (2007) 7892–7898
ꢀ
molecular sieves after the reagent became blue. Some re-
agents were re-distilled before use. The common solvents
were used directly without further purification. Thin-layer
chromatography (TLC) was performed on silica gel 60
F254 glass backed plates. Melting points were measured on
The resulting reaction mixture was stirred at 0 C for needful
time. The reaction mixture was extracted with ethyl acetate.
The combined organic layers were washed with saturated
brine, dried over Na SO , and concentrated. The residue
was subjected directly to flash silica gel chromatographic
column using petroleum–ethyl acetate as the eluent to afford
the corresponding pure aldol adducts.
2
4
an X -type micro-melting point apparatus and were uncor-
4
rected. Mass spectrometric analyses were performed on
1
13
a ZAB-2F spectrometer. H NMR spectra and C NMR
spectra were recorded on a Varian Mercury-300 spectrome-
ter in needful D-reagents with tetramethylsilane (TMS) as an
internal standard. The maximum wavelength values were re-
corded with a TU-1901-type UV-spectrophotometer. Enan-
tiomeric excess values of aldol products were determined
by analytical HPLC using Daicel Chiralpak AD or AS ana-
lytical columns with 2-propanol in hexanes as the eluent.
4.3.1. 2-[Hydroxyl(pyridin-4-yl)methyl]cyclohexanone
(8a). White powder; mp 108–109 C; 93% yield; 86% ee
ꢀ
(anti) [Daicel Chiralpak AD-H column, n-hexane/iso-
propanol¼92:8, 1.0 mL/min, 254 nm; t (anti)¼29.79 min
R
(major) and 27.10 min, t (syn)¼22.81 min and 19.68 min
R
1
(major)]; H NMR (300 MHz, CDCl ): d 8.55–8.59 (m,
3
2H), 7.24–7.27 (m, 2H), 4.77–5.39 (dd, 1H), 2.31–2.64
(
m, 3H), 2.09–2.14 (m, 1H), 1.82–1.86 (m, 1H), 1.59–1.76
(m, 3H), 1.34–1.56 (m, 1H); HRMS for C H NO
2
4
.2. Preparation of catalysts 1–5
1
2
15
(M+H): calcd 206.11756, obsd 206.11784.
The synthesis of catalysts 1–5 were carried out according to
the standard method of dipeptide preparation.
1
8
4.3.2. 2-[Hydroxyl(4-nitrophenyl)methyl]cyclohexanone
1
9,20
ꢀ
White powder; mp 129–130 C; 93% yield; 97%
ee (anti) [Daicel Chiralpak AD-H column, n-hexane/iso-
(8b).
ꢀ
25
D
4
.2.1. Pro–Phe (1). White powder; mp 236–237 C; [a]
1
ꢂ50 (c 2, HCl aq); H NMR (300 MHz, D O): d 7.11–
propanol¼92:8, 1.0 mL/min, 268 nm; t (anti)¼45.64 min
2
R
7
1
.23 (m, 5H), 4.26–4.30 (q, J¼5.1 Hz, 1H), 4.05–4.08 (m,
(major) and 42.01 min, t (syn)¼37.83 min and 26.57 min
R
1
H), 3.17–3.22 (m, 2H), 3.04 (q, J¼5.1 Hz, 1H), 2.79 (q,
(major)]; H NMR (300 MHz, CDCl ): d 8.20–8.24 (m,
3
J¼9.0 Hz, 1H), 2.15–2.28 (m, 1H), 1.82–1.88 (m, 3H);
2H), 7.48–7.54 (m, 2H), 4.90 (d, J¼8.1 Hz, 1H), 4.09 (s,
+
ESI-MS m/z 263.2 (M +1).
1H), 2.32–2.64 (m, 3H), 2.08–2.16 (m, 1H), 1.82–1.86 (m,
1
H), 1.35–1.73 (m, 4H).
ꢀ
25
D
4
.2.2. Pro–Leu (2). White powder; mp 235–237 C; [a]
1
ꢂ55 (c 0.4, HCl aq); H NMR (300 MHz, DMSO-d ):
4.3.3. 2-[Hydroxyl(2-nitrophenyl)methyl]cyclohexanone
ꢀ
6
2
0
d 8.01–8.04 (m, 1H), 5.76 (s, 1H), 3.58–3.64 (m, 1H),
(8c). Yellow powder; mp 116–118 C; 88% yield; 89%
ee (anti) [Daicel Chiralpak AD-H column, n-hexane/iso-
1
6
.17–1.88 (m, 7H), 1.09 (t, J¼7.2 Hz, 2H), 0.82–0.87 (m,
+
H); ESI-MS m/z 229.2 (M +1).
propanol¼92:8, 1.0 mL/min, 209 nm; t (anti)¼27.55 min
R
1
and 25.38 min (major)]; H NMR (300 MHz, CDCl ):
3
ꢀ
25
D
4
.2.3. Pro–Ile (3). White powder; mp 231–232 C; [a]
d 7.84 (d, J¼7.8 Hz, 1H), 7.77 (d, J¼7.8 Hz, 1H), 7.64 (t,
J¼7.2 Hz, 1H), 7.40–7.46 (m, 1H), 5.44 (d, J¼7.2 Hz,
1H), 4.11 (br, 1H), 2.73–2.81 (m, 1H), 2.29–2.48 (m, 2H),
2.04–2.14 (m, 1H), 1.55–1.86 (m, 5H).
1
ꢂ44 (c 2, HCl aq); H NMR (300 MHz, CD OD): d 4.23–
3
4
1
.27 (m, 2H), 2.37–2.44 (m, 2H), 1.89–2.14 (m, 4H),
.51–1.59 (m, 1H), 1.12–1.22 (m, 1H), 0.89–0.96 (m, 6H);
+
ESI-MS m/z 229.2 (M +1).
4
.3.4. 2-[Hydroxyl(3-nitrophenyl)methyl]cyclohexanone
ꢀ
ꢀ
25
D
20
4
.2.4. Pro–Tyr (4). White powder; mp 232–234 C; [a]
(8d). White powder; mp 69–71 C; 89% yield; 80% ee
(anti) [Daicel Chiralpak AD-H column, n-hexane/iso-
1
ꢂ26 (c 2, HCl aq); H NMR (300 MHz, DMSO-d6):
d 9.20 (s, 1H), 8.12 (s, 1H), 6.92 (d, J¼8.4 Hz, 2H), 6.62
propanol¼92:8, 1.0 mL/min, 263 nm; t (anti)¼31.87 min
R
(
2
1
d, J¼8.4 Hz, 2H), 4.31 (s, 1H), 3.59–3.63 (m, 1H), 2.82–
and 24.65 min (major), t (syn)¼21.82 min (major) and
R
1
.98 (m, 3H), 2.67–2.75 (m, 1H), 1.92–1.98 (m, 1H),
.51–1.66 (m, 3H); ESI-MS m/z 278.2 (M).
19.65 min]; H NMR (300 MHz, CDCl ): d 8.15–8.22 (m,
3
2H), 7.67 (d, J¼7.5 Hz, 1H), 7.53 (t, J¼7.8 Hz, 1H), 4.90
(
d, J¼8.4 Hz, 1H), 4.14 (d, J¼2.4, 1H), 2.58–2.67 (m,
ꢀ
25
D
4
.2.5. Pro–Trp (5). White powder; mp 183–184 C; [a]
1H), 2.32–2.54 (m, 2H), 2.09–2.16 (m, 1H), 1.82–1.86 (m,
1H), 1.36–1.71 (m, 4H).
1
ꢂ32 (c 1, HCl aq); H NMR (300 MHz, DMSO-d6):
d 10.87 (s, 1H), 8.36 (d, J¼7.2 Hz, 1H), 7.51 (d,
J¼7.8 Hz, 1H), 7.32 (d, J¼7.8 Hz, 1H), 6.94–7.10 (m,
4.3.5. 2-[Hydroxyl(4-cyanophenyl)methyl]cyclohexa-
ꢀ
2
0
3
3
1
(
1
2
H), 4.48 (q, J¼5.4 Hz, 1H), 3.77 (q, J¼5.7 Hz, 1H),
none (8e). White powder; mp 82–83 C; 94% yield;
85% ee (anti) [Daicel Chiralpak AD-H column, n-hexane/
.06–3.24 (m, 2H), 2.87–2.95 (m, 1H), 2.75–2.83 (m, 1H),
.99–2.11 (m, 1H), 1.57–1.73 (m, 3H);
1
3
C NMR
isopropanol¼92:8, 1.0 mL/min,267 nm;t (anti)¼32.54 min
R
75 MHz, DMSO-d ): d 173.1, 171.4, 136.0, 127.3, 123.6,
6
20.9, 118.3, 111.3, 109.6, 59.4, 53.0, 48.6, 46.1, 29.9,
7.1, 24.7; ESI-MS m/z 301.1 (M).
(major) and 26.75 min, t (syn)¼23.80 min and 20.80 min
R
1
(major)]; H NMR (300 MHz, CDCl ): d 7.65 (d, J¼8.1 Hz,
3
2H), 7.43 (d, J¼8.1 Hz, 2H), 4.84 (d, J¼8.4 Hz, 1H), 4.07
(s, 1H), 2.47–2.62 (m, 2H), 2.31–2.41 (m, 1H), 2.08–2.15
4
.3. General procedure for aldol reactions
(m, 1H), 1.81–1.83 (m, 1H), 1.49–1.73 (m, 3H), 1.32–1.41
m, 1H).
(
To a solution of aldehyde acceptor (1 mmol) and ketone
donor (4 mmol) in 1.5 mL of H O were added the catalyst
4.3.6. 2-[Hydroxyl(phenyl)methyl]cyclohexanone
ꢀ
Light yellow powder; mp 99–101 C; 72% yield;
2
2
0,21
(
20 mol %), base (20 mol %), and surfactant (5 mol %).
(8f).

M. Lei et al. / Tetrahedron 63 (2007) 7892–7898
7897
1
8
8% ee (anti) [Daicel Chiralpak AD-H column, n-hexane/
(major)]; H NMR (300 MHz, CDCl ): d 7.96 (d,
3
isopropanol¼92:8, 1.0 mL/min, 215 nm; tR (anti)¼
J¼8.1 Hz, 1H), 7.85 (d, J¼7.8 Hz, 1H), 7.75 (t, J¼7.8 Hz,
1H), 7.52 (t, J¼7.8 Hz, 1H), 5.68 (d, J¼4.8 Hz, 1H), 5.55
(s, 1H), 1.93–2.43 (m, 5H), 1.62–1.68 (m, 2H).
2
1
7
2
1
8.44 min and 24.63 min (major), t (syn)¼22.81 min and
R
1
9.43 min (major)]; H NMR (300 MHz, CDCl ): d 7.31–
3
.35 (m, 5H), 4.77 (d, J¼9.0 Hz, 1H), 3.95 (br, 1H), 2.57–
.66 (m, 1H), 2.05–2.51 (m, 2H), 1.56–1.58 (m, 1H),
.48–1.53 (m, 4H), 1.27–1.32 (m, 1H).
4.3.13. 2-[Hydroxyl(3-nitrophenyl)methyl]cyclopenta-
ꢀ
2
3
none (8m). White powder; mp 72–74 C; 80% yield;
1% ee (anti), 72% ee (syn) [Daicel ChiralpakAD-H column,
8
4
.3.7. 2-[Hydroxy(6-nitro-1,3-dihydroisobenzofuran-5-
yl)methyl]cyclohexanone (8g). Light yellow powder; mp
65–166 C; 68% yield; 95% ee (anti) [Daicel Chiralpak
n-hexane/isopropanol¼92:8, 1.0 mL/min, 269 nm; t (anti)¼
R
34.55 min and 23.91 min (major), t (syn)¼19.85 min and
R
ꢀ
1
1
17.64 min (major)]; H NMR (300 MHz, CDCl ): d 8.24 (s,
3
AD-H column, n-hexane/isopropanol¼92:8, 1.0 mL/min,
1H), 8.11–8.19 (m, 1H), 7.69 (t, J¼7.8 Hz, 1H), 7.50–7.57
(m, 1H), 4.82–5.43 (dd, J¼3.3 Hz, 1H), 2.71 (s, 1H), 1.91–
2.53 (m, 5H), 1.70–1.80 (m, 2H).
2
14 nm; t (anti)¼58.83 min and 37.32 min (major), t
R
R
1
(
(
syn)¼33.22 min (major) and 30.14 min];
H NMR
300 MHz, CDCl ): d 7.61 (s, 1H), 7.26 (s, 1H), 6.22 (s,
3
2
2
H), 5.69 (d, J¼7.5 Hz, 1H), 5.57 (dd, 1H), 2.39–2.51 (m,
4.3.14. 2-[Hydroxyl(4-nitrophenyl)methyl]cyclopenta-
2
3
ꢀ
H), 2.17–2.26 (m, 1H), 1.92–2.09 (m, 4H); HRMS for
none (8n). Light yellow powder; mp 88–90 C; 85% yield;
79% ee (anti), 62% ee (syn) [Daicel Chiralpak AD-H col-
umn, n-hexane/isopropanol¼92:8, 1.0 mL/min, 251 nm;
C H NO (M+Na): calcd 316.07916, obsd 316.07943.
1
4
15
6
4
.3.8. 2-[Hydroxyl(4-methoxyphenyl)methyl]cyclohexa-
ꢀ
t
(anti)¼26.20 min (major) and 25.20 min, t (syn)¼
R
R
2
1
1
none (8h). White powder; mp 74–76 C; 67% yield;
3% ee (anti) [Daicel Chiralpak AD-H column, n-hexane/
19.36 min and 14.40 min (major)]; H NMR (300 MHz,
CDCl ): d 8.20–8.24 (m, 2H), 7.51–7.56 (m, 2H), 4.78–
5.43 (m, 1H), 1.52–2.62 (m, 7H).
8
3
isopropanol¼92:8, 1.0 mL/min, 218 nm; tR (anti)¼
2
1
7
3
8.10 min (major) and 27.35 min, t (syn)¼18.64 min and
R
1
20
5.94 min (major)]; H NMR (300 MHz, CDCl ): d 7.22–
3
4.3.15. 4-(4-Nitrophenyl)-4-hydroxy-2-butanone (8o).
ꢀ
.26 (m, 2H), 6.86–6.90 (m, 2H), 4.74 (d, J¼8.7 Hz, 1H),
White powder; mp 59–61 C; 94% yield; 58% ee [Daicel
Chiralpak AD-H column, n-hexane/isopropanol¼92:8,
.92 (s, 1H), 3.80 (s, 3H), 2.31–2.64 (m, 3H), 2.05–2.13
(
m, 1H), 1.48–1.81 (m, 4H), 1.19–1.33 (m, 1H).
1.0 mL/min, 254 nm; t ¼43.72 min (major) and 42.09 min];
R
1
H NMR (300 MHz, CDCl ): d 8.21 (d, J¼8.7 Hz, 2H), 7.54
3
4
.3.9. 2-[Hydroxyl(2-chlorophenyl)methyl]cyclohexa-
ꢀ
(d, J¼8.7 Hz, 2H), 5.25–5.29 (m, 1H), 3.57 (d, J¼3.3 Hz,
2
0
none (8i). White powder; mp 89–91 C; 73% yield; 90%
ee (anti) [Daicel Chiralpak AD-H column, n-hexane/iso-
1H), 2.84–2.87 (m, 2H), 2.22 (s, 3H).
2
4
propanol¼92:8, 1.0 mL/min, 210 nm; t (anti)¼15.63 min
4.3.16. 4-Hydroxy-5-methylhexan-2-one (8p). Yellow
oil; 81% yield; 67% ee [Daicel Chiralpak AD-H column,
R
1
and 13.64 min (major)]; H NMR (300 MHz, CDCl ):
3
d 7.18–7.56 (m, 4H), 5.34 (dd, J¼8.1 Hz, 1H), 4.10 (br, 1H),
n-hexane/isopropanol¼92:8, 1.0 mL/min, 280 nm; t ¼
R
1
1
.53–2.69 (m, 9H).
11.4 min and 10.4 min (major)]; H NMR (300 MHz,
CDCl ): d 3.79–3.85 (m, 1H), 2.45–2.66 (m, 3H), 2.20 (s,
3H), 1.63–1.74 (m, 1H), 0.93 (t, 6H).
3
4
.3.10. 2-[Hydroxyl(5-nitrofuran-2-yl)methyl]cyclohexa-
none (8j). Yellow oil; 90% yield; 85% ee (anti); 83% ee
syn) [Daicel Chiralpak AD-H column, n-hexane/iso-
(
4.3.17. 1-(4-Nitrophenyl)-5-methyl-1-hydroxy-3-hexa-
ꢀ
propanol¼92:8, 1.0 mL/min, 316 nm; t (anti)¼27.31 min
none (8q). Light yellow powder; mp 70–72 C; 67% yield;
83% ee (anti), 76% ee (syn) [Daicel Chiralpak AD-H
column, n-hexane/isopropanol¼92:8, 1.0 mL/min, 269 nm;
R
and 22.83 min (major), t (syn)¼17.48 min and 18.88 min
R
1
(
1
1
5
major)]; H NMR (300 MHz, CDCl ): d 7.30 (q, J¼3.9 Hz,
3
H), 6.59–6.61 (m, 1H), 4.81–5.37 (dd, 1H), 2.92–3.02 (m,
H), 2.40–2.46 (m, 2H), 2.12–2.16 (m, 1H), 1.60–1.94 (m,
H); HRMS for C H NO (M+H): calcd 2240.08665,
t
31.08 min and 25.42 min (major)]; H NMR (300 MHz,
(anti)¼46.48 min (major) and 34.41 min, t (syn)¼
R
R
1
CDCl ): d 8.20–8.23 (m, 2H), 7.50–7.53 (m, 2H), 4.90 (d,
3
1
1
13
5
obsd 240.08710.
J¼8.4 Hz, 2H), 4.09 (s, 1H), 2.48–2.64 (m, 2H), 2.32–2.42
(
m, 1H), 2.09–2.15 (m, 1H), 1.82–1.85 (m, 1H), 1.26–1.71
4
.3.11. (E)-2-(1-Hydroxy-3-phenylallyl)cyclohexanone
ꢀ
(m, 6H); HRMS for C H NO (M+H): calcd 252.12358,
13 17 4
obsd 252.12399.
2
2
(
8k). White powder; mp 119–121 C; 81% yield; 72% ee
anti) [Daicel Chiralpak AD-H column, n-hexane/iso-
(
propanol¼92:8, 1.0 mL/min, 255 nm; t (anti)¼21.63 min
R
Acknowledgements
and 18.64 min (major), t (syn)¼17.65 min and 15.01 min
R
1
(
major)]; H NMR (300 MHz, CDCl ): d 7.38 (dd, 2H), 7.31
3
This research was supported by the funds of National Natu-
ral Science Foundation of China (no. 20572004) and the
Major State Basic Research Development Program (Grant
no. 2004CB719900).
(
6
3
t, J¼7.8 Hz, 2H), 7.20–7.26 (m, 1H), 6.58–6.66 (m, 1H),
.15–6.25 (m, 1H), 4.43 (t, J¼4.8 Hz, 1H), 2.31–2.59 (m,
H),2.07–2.13(m, 2H), 1.87–1.94(m,1H),1.63–1.78(m, 3H).
4
.3.12. 2-[Hydroxyl(2-nitrophenyl)methyl]cyclopenta-
2
3
none (8l). Yellow oil; 82% yield; 88% ee (anti); 40% ee
syn) [Daicel Chiralpak AD-H column, n-hexane/iso-
Supplementary data
(
propanol¼92:8, 1.0 mL/min, 209 nm; t (anti)¼25.03 min
Supplementary data associated with this article can be found
in the online version, at doi:10.1016/j.tet.2007.05.077.
R
and 23.46 min (major), t (syn)¼20.00 min and 17.13 min
R

7898
M. Lei et al. / Tetrahedron 63 (2007) 7892–7898
References and notes
9. Font, D.; Jimeno, C.; Pericas, M. A. Org. Lett. 2006, 8,
653.
4
1
1
1
1
1
1
0. Chen, X. H.; Luo, S. W.; Tang, Z.; Cun, L. F.; Mi, A. Q.; Jiang,
Y. Z.; Gong, L. Z. Chem.—Eur. J. 2007, 13, 689.
1. Shi, L. X.; Sun, Q.; Ge, Z. M.; Zhu, Y. Q.; Cheng, T.-M.; Li,
R. T. Synlett 2004, 2215.
2. Tang, Z.; Yang, Z. H.; Cun, L. F.; Gong, L. Z.; Mi, A. Q.; Jiang,
Y. Z. Org. Lett. 2004, 6, 2285.
3. Akagawa, K.; Sakamoto, S.; Kudo, K. Tetrahedron Lett. 2005,
1
2
. (a) Machajewski, T. D.; Wong, C. H. Angew. Chem., Int. Ed.
2
000, 39, 1352; (b) Mukaiyama, T. Angew. Chem., Int. Ed.
004, 43, 5590; (c) Sakthivel, K.; Notz, W.; Bui, T.; Barbas,
2
C. F., III. J. Am. Chem. Soc. 2001, 123, 5260.
. (a) Reggelin, M.; Brenig, V.; Zur, C. Org. Lett. 2000, 2, 531; (b)
Benaglia, M.; Celentano, G.; Cozzi, F. Adv. Synth. Catal. 2001,
343, 171; (c) List, B.; Pojarliev, P.; Castello, C. Org. Lett. 2001,
3, 573; (d) Oisaki, K.; Zhao, D.; Kanai, M.; Shibasaki, M.
4
6, 8185.
4. Tsogoeva, S. B.; Wei, S. W. Tetrahedron: Asymmetry 2005,
6, 1947.
J. Am. Chem. Soc. 2006, 128, 7164; (e) Trost, B. M.; Ito, H.
J. Am. Chem. Soc. 2000, 122, 12003; (f) Miao, W. S.; Chan,
T. H. Adv. Synth. Catal. 2006, 348, 1711; (g) Bassan, A.;
Zou, W. B.; Reyes, E.; Himo, F.; C ꢀo rdova, A. Angew. Chem.,
Int. Ed. 2005, 44, 7028; (h) Gryko, D.; Lipi ꢀn ski, R. Adv.
Synth. Catal. 2005, 347, 1948; (i) Din ꢀe r, P.; Amedjkouh, M.
Org. Biomol. Chem. 2006, 2091.
1
5. (a) C ꢀo rdova, A.; Zou, W. B.; Dziedzic, P.; Ibrahem, I.; Reyes,
E.; Xu, Y. M. Chem.—Eur. J. 2006, 12, 5383; (b) Zou, W. B.;
Ibrahem, I.; Dziedzic, P.; Sund ꢀe n, H.; C ꢀo rdova, A. Chem.
Commun. 2005, 4946; (c) Dziedzic, P.; Zou, W. B.; H ꢀa fren,
J.; C ꢀo rdova, A. Org. Biomol. Chem. 2006, 4, 38.
1
6. Jiang, Z. Q.; Liang, Z. A.; Wu, X. Y.; Lu, Y. X. Chem. Commun.
3
4
. (a) Tang, Z.; Yang, Z. H.; Chen, X. H.; Cun, L. F.; Mi, A. Q.;
Jiang, Y. Z.; Gong, L. Z. J. Am. Chem. Soc. 2005, 127, 9285;
2
006, 2801.
7. (a) List, B.; Lerner, R. A.; Barbas, C. F., III. Org. Lett. 1999, 1,
53; (b) Flanagan, M. E.; Jacobsen, J. R.; Sweet, E.; Schultz,
1
(
b) 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,
262; (c) Raj, M.; Vishnumaya; Ginotra, S. K.; Singh, V. K.
3
P. G. J. Am. Chem. Soc. 1996, 118, 6078; (c) Fessner, W. D.;
Sinerius, G.; Schneider, A.; Dreyer, M.; Schulz, G. E.; Badia,
J.; Aguilar, J. Angew. Chem., Int. Ed. Engl. 1991, 30, 555; (d)
Ahn, M.; Pietersma, A. L.; Schofield, L. R.; Parker, E. J.
Org. Biomol. Chem. 2005, 4046; (e) Lamble, H. J.; Danson,
M. J.; Hough, D. W.; Bull, S. D. Chem. Commun. 2004, 124;
5
Org. Lett. 2006, 8, 4097; (d) Saito, S.; Kobayashi, S. J. Am.
Chem. Soc. 2006, 128, 8704.
. (a) Torii, H.; Nakadai, M.; Ishihara, K.; Saito, S.; Yamamoto,
H. Angew. Chem., Int. Ed. 2004, 43, 1983; (b) C ꢀo rdova, A.;
Zou, W. B.; Ibrahem, I.; Reyes, E.; Engqvist, M.; Liao,
W. W. Chem. Commun. 2005, 3586; (c) C ꢀo rdova, A.; Notz,
W.; Barbas, C. F., III. Chem. Commun. 2002, 3024; (d)
Kobayashi, S.; Mori, Y.; Nagayama, S.; Manabe, K. Green
Chem. 1999, 175.
. (a) Reymond, J. L.; Chen, Y. J. Org. Chem. 1995, 60, 6970; (b)
Dickerson, T. J.; Janda, K. D. J. Am. Chem. Soc. 2000, 122,
7386; (c) See Ref. 4c; (d) Chimni, S. S.; Mahajan, D.; Babu,
V. V. S. Tetrahedron Lett. 2005, 46, 5617.
(f) Juhl, K.; Gathergood, N.; Jørgensen, K. A. Chem.
Commun. 2000, 2211.
1
1
2
8. Huang, W. D.; Chen, C. Q. The Synthesis of Multipeptides;
Science Ed.: Beijing, 1985; pp 102–108.
9. Fernandez-Lopez, R.; Kofoed, J.; Machuqueiro, M.; Darbre, T.
Eur. J. Org. Chem. 2005, 24, 5268.
0. Chen, J. R.; Lu, H. H.; Li, X. Y.; Cheng, L.; Wan, J.; Xiao, W. J.
Org. Lett. 2005, 20, 4543.
5
2
2
1. Kobayashi, S.; Hachiya, I. J. Org. Chem. 1994, 59, 3590.
2. Denmark, S. E.; Winter, S. B. D.; Su, X. P.; Wong, K. T. J. Am.
Chem. Soc. 1996, 118, 7404.
6
. (a) Hayashi, Y.; Sumiya, T.; Takahashi, J.; Gotoh, H.;
Urushima, T.; Shoji, M. Angew. Chem., Int. Ed. 2006, 45,
958; (b) Hayashi, Y.; Aratake, S.; Okano, T.; Takahashi, J.;
2
3. Peng, Y. Y.; Ding, Q. P.; Li, Z.; Wang, P. G.; Cheng, J. P.
Tetrahedron Lett. 2003, 44, 3871.
4. Chandrasekhar, S.; Ramakrishna, N. R.; Shameem, S. S.;
Narsihmulu, Ch.; Venkatram, K. R. Tetrahedron 2006, 62,
Sumiya, T.; Shoji, M. Angew. Chem., Int. Ed. 2006, 45, 5527.
. Mase, N.; Nakai, Y.; Ohara, N.; Yoda, H.; Takabe, K.; Tanaka,
F.; Barbas, C. F., III. J. Am. Chem. Soc. 2006, 128, 734.
. Wu, Y. Y.; Zhang, Y. Z.; Yu, M. L.; Zhao, G.; Wang, S. W. Org.
Lett. 2006, 8, 4417.
7
8
2
3
38.