Facile preparation of optically pure diamines and their applications in asymmetric aldol reactions

Article abstract of DOI:10.1016/j.tetlet.2008.10.085

A family of optically pure diamines with tertiary-primary amine motif has been synthesized from optically pure binaphthol and amino acids. The catalysts are highly tunable in structure and has demonstrated high efficiency in direct aldol reactions. Thus, a variety of aldehydes or methyl 2-oxoacetates reacted with acetone in the presence of 10 mol % of catalyst and 20 mol % TFA, furnishing the desired alcohols in up to 99% yield with excellent enantioselectivities (up to 96% ee).

Full text of DOI:10.1016/j.tetlet.2008.10.085

Tetrahedron Letters 49 (2008) 7434–7437
Contents lists available at ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Facile preparation of optically pure diamines and their applications
in asymmetric aldol reactions
a
b,
a
a
Quan-Zhong Liu a, , Xue-Lian Wang , Shi-Wei Luo , Bao-Lei Zheng , Da-Bin Qin
*
*
a Laboratory of Applied Chemistry and Pollution Control Technology, College of Chemistry and Chemical Engineering, China West Normal University, Nanchong 637002, China
b Hefei National Laboratory for Physical Sciences at the Microscale and Department of Chemistry, University of Science and Technology of China, Hefei 230026, China
a r t i c l e i n f o
a b s t r a c t
Article history:
A family of optically pure diamines with tertiary–primary amine motif has been synthesized from opti-
cally pure binaphthol and amino acids. The catalysts are highly tunable in structure and has demon-
strated high efficiency in direct aldol reactions. Thus, a variety of aldehydes or methyl 2-oxoacetates
reacted with acetone in the presence of 10 mol % of catalyst and 20 mol % TFA, furnishing the desired
alcohols in up to 99% yield with excellent enantioselectivities (up to 96% ee).
Received 25 July 2008
Revised 14 October 2008
Accepted 17 October 2008
Available online 22 October 2008
Ó 2008 Elsevier Ltd. All rights reserved.
The advantages of organocatalysis have been demonstrated in
asymmetric transformations by the facile preparation of the cata-
lysts, the mild reaction conditions, and by their environmentally
benign aspects as compared to metal catalysis.1 Chiral amines such
as cinchona, and 1,2-cyclohexane-1,2-diamine or their derivatives
have received great attention for their unique activation modes
and high efficiencies.2 Reactions catalyzed by nucleophilic chiral
amines such as ketene acylation, b-lactam formation, Baylis–
Hillman reactions and other transformations were developed over
the past few years.3 Recently, chiral amines featured with a pri-
mary–tertiary amine structure have been widely employed in
asymmetric reactions. In these asymmetric transformations, the
to describe a facile synthesis of novel chiral diamines (Fig. 1) using
optically pure binaphthol and chiral amino acids, and their applica-
tion in enantioselective aldol reactions based on the following con-
siderations: (1) both enantiomers of binaphthol and amino acids
are commercially available, and optically pure binaphthol has
shown excellent performance in a series of asymmetric transfor-
mations;7 (2) high enantioselectivities can be obtained, when the
two stereocenters in the synthesized diamines are matched; and,
especially, (3) the amines are highly tunable with respect to struc-
tural modification, simplifying the introduction of substituents at
different positions of binaphthol. Furthermore, chiral amino acids
are readily available.
chiral amines act as bifunctional catalysts, deprotonating the
of carbonyl compounds to form enamines or condensing with car-
bonyl functionalities of ,b-unsaturated compounds to form ,b-
a
-H
The syntheses of catalysts 1a–d are shown in Scheme 1. The
readily prepared chiral amine 28 was condensed with N-Boc pro-
tected (S)-phenyl glycine in the presence of stoichiometric EDCI
affording the corresponding amides in 93% yield. After Boc depro-
tection with TFA in CH2Cl2 and subsequent reduction of amide car-
bonyl group using borane (BH3–Me2S) in THF afforded the desired
diamines in 70–89% yield in two steps.9 Attempts to obtain the
product using other reduction methods such as LiAlH4, DIBAL-H,
and NaBH4–I2 were unsuccessful.
a
a
unsaturated imines in the presence of an achiral Brønsted acid.
Recently, 9-amino(9-deoxy)epi-quinine in combination with
achiral acids was reported to be an effective catalyst for the asym-
metric conjugate addition of carbon-centered nucleophiles to sim-
ple enones, and aldol reactions between aldehydes and enones via
iminium-ion catalysis.4 In 2007, Chen reported a highly efficient
aldol reaction catalyzed by chiral diamines derived from optically
pure cyclohexane–diamine.5 All these aforementioned amines fea-
ture a tertiary–primary amine structure in the catalysts. We also
disclosed an enantioselective aldol reaction catalyzed by a cincho-
nine-derived amine.6 However, the amines used in the asymmetric
aldol reactions were mostly derived from proline, cinchona and
1,2-cyclohexanediamine. They were either difficult to synthesize
or modulate the reactivity through structure modifications. These
shortcomings restricted their further applications. Herein, we wish
R
N
H2N
N
H
H2N
R
N
1
11
* Corresponding authors.
E-mail address: quanzhongliu@sohu.com (Q.-Z. Liu).
Figure 1. Structure of amines derived from Cinchona and new amines.
0040-4039/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2008.10.085

Q.-Z. Liu et al. / Tetrahedron Letters 49 (2008) 7434–7437
7435
O
R
O
R
R
O
HO
NHBoc
N
TFA, CH2Cl2
NH
N
NHBoc
NH2
EDCI, CH2Cl2
R
R
R
4
3
2
F
R
F
BH3-Me2S
1a, R = H
1c,
R =
R =
CF3
N
F
THF, Reflux
NH2
1b,
R =
1d,
CF3
R
1
Scheme 1. Synthesis of novel diamines.
To develop the potential applications of the synthesized dia-
mines in organocatalysis, the chiral diamines were then surveyed
in the direct enantioselective aldol reactions between ketones
and aromatic aldehydes. The aldol reaction between 4-nitrobenzal-
dehyde and acetone was chosen as the model reaction (Table 1). 4-
Nitrobenzaldehyde reacted with acetone smoothly, affording the
product in 50% yield with 91% ee (in the presence of 10 mol % 1a
and 15 mol % TFA (entry 6)). (S)-BINOL-derived catalyst (S0,R)-1a
afforded 81% ee (55% yield) with the same configuration (R). Intro-
duction of substituents such as phenyl, 3,5-trifluoromethylphenyl,
and 3,4,5-trifluorophenyl (1b, 1c, and 1d) led to very low enanti-
oselectivities (18–25% ee, entries 8–10). It seems that both binaph-
thyl and amino motif have significant impacts on the reaction.
However, the configuration of amino motif determined the config-
uration of the product. A comparison of the effects of acid revealed
that TFA was the best choice (entries 1–3 vs 6). The amount of TFA
used considerably affected the reactivity of the catalyst. Lowering
the amount of TFA was beneficial for the yield of reaction, but
was deleterious for the enantioselectivity (entries 4–6 and 11–
12). The reaction was dependent on the solvents used, less polar
solvents such as THF, ether, and DCM afforded high ee values, al-
beit in lower yields (entries 13, 15, 17, 18). Polar solvents were del-
eterious for the enantioselectivities (entries 14, 16, 19, 20).
Based on this study, the optimal reaction condition was
10 mol % of 1a in combination with 20 mol % TFA as catalyst and
neat acetone as the solvent (see Supplementary data).10 Various
aromatic aldehydes reacted with acetone, and the results are sum-
marized in Table 2. These trials indicated that the reaction was dra-
matically dependent on the electron effect of the substituents. For
example, 4- or 3-nitrobenzaldehydes and 4-cyanobenzaldehyde
underwent aldol reactions in moderate yields (43–56%) and excel-
lent enantioselectivities (91–94% ee, entries 1–3, Table 2). Less
electron-deficient aldehydes such as 4-trifluoromethyl and 2-chlo-
robezaldehydes afforded products in lower enantioselectivities
(entries 4 and 6). 2-Nitrobenzaldehyde gave only 86% ee (entry
5) compared to that of 4-nitrobenzaldehyde, perhaps due to the
Table 1
Optimization of aldol reactions between aromatic aldehydes and ketonesa
OH
O
O
O
10 mol% cat
+
acid
neat
O2N
O2N
5
6
7
Entry Cat.
Solvent Temperature Acid (mol %)
Yield (%) ee (%)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
1a
1a
1a
1a
1a
1a
Neat
Neat
Neat
Neat
Neat
Neat
25
25
25
25
25
25
25
25
25
25
25
25
25
25
TfOH (15%)
TsOH (15%)
ClCH2COOH (15%) 94
87
6
64
50
43
62
86
91
81
18
25
28
94
90
93
54
89
27
95
93
68
61
89
73
72
Table 2
Reactions between aldehydes and ketonesa
TFA (5%)
98
76
50
55
52
68
58
43
38
42
52
29
35
44
38
35
63
44
67
38
O
O
TFA (10%)
TFA (15%)
TFA (15%)
TFA (15%)
TFA (15%)
TFA (15%)
TFA (20%)
TFA (25%)
TFA (20%)
TFA (20%)
TFA (20%)
TFA (20%)
TFA (20%)
TFA (20%)
TFA (20%)
TFA (20%)
TFA (20%)
TFA (20%)
TFA (20%)
O
HO
1a 10 mol%
O
+
+
R
R
H
S0,S-1a Neat
R
20 mol% TFA
8
1b
1c
1d
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
Neat
Neat
Neat
Neat
Neat
THF
DMSO
Hexane 25
H2O
CH2Cl2
Et2O
EtOH
DMF
Neat
Neat
Neat
5
Entry
7
R
Yield (%)
ee (%)
Configurationb
7 (8)
1
4-NO2C6H4
3-NO2C6H4
4-CNC6H4
2-ClC6H4
2-NO2C6H4
4-CF3C6H4
4-CH3C6H4
4-NO2C6H4
43 (55)
56 (41)
50 (43)
58 (40)
62 (30)
41 (40)
11 (9)
95
94
91
94
90
86
85
66
82
R
R
R
R
R
R
R
—
2
3a
4
5
6
25
25
25
25
25
40
0
7
8c
a
Unless otherwise stated, the reaction was carried out at 25 °C with 0.25 mmol
of methyl 2-oxoacetates and 1.0 mL (9.6 mmol) of acetone in the presence of
10 mol % of catalyst 1a in combination with 20 mol % TFA. The enantioselectivities
were determined by chiral AD–H.
ꢀ18
b
a
The configuration was determined by the comparison of retention time repor-
All reactions were carried out with 0.1 mmol of aldehydes and 0.5 mL
ted in the literature.5
(4.8 mmol) of acetone at 0 °C. The enantioselectivity was measured using chiral
AD–H.
c
Cyclohexanone was used.

7436
Q.-Z. Liu et al. / Tetrahedron Letters 49 (2008) 7434–7437
steric hindrance. The substrates with electron-donating groups at
the aromatic ring were less satisfactory. For example, 4-methyl-
benzaldehyde afforded the product in only 11% yield after long
reaction time with moderate enantioselectivity (66% ee, entry 7).
When cyclohexanone was used to replace acetone in the system,
the anti-isomer was favorably formed (95% yield, 82% ee, dr 94:6,
entry 8). A careful investigation found that the low yield of aldol
reactions between aldehydes and acetone resulted from dehydra-
aldehydes and methyl 2-oxo-acetates reacted with acetone afford-
ing the corresponding b-hydroxy ketones in high yields with excel-
lent stereoselectivities. The studies on mechanism of direct aldol
reactions and further application of the catalysts and their deriva-
tives in asymmetric transformations are under way, and will be re-
ported in due course.
Acknowledgments
tion of the aldol product to form the corresponding
rated ketone 8.
a,b-unsatu-
We are grateful for the financial support from National Natural
Science Foundation of China (No. 20772097) and Sichuan Provin-
cial Science Foundation for Outstanding Youth (No. 05ZQ026-
008) and Key Project of the Education Department of Sichuan Prov-
ince (No. 2006A081).
The use of catalyst 1a can be extended to the direct aldol reac-
tion of methyl 2-oxo-2-phenylacetate and ketones. This reaction
was investigated by Feng’s group using cyclohexanone-1,2-dia-
mine-derived prolinamide as catalyst.11 Although chiral tertiary
alcohols are important intermediates in pharmaceutical industry,12
their syntheses are rarely reported. The same reaction was also re-
ported by other groups.13 In the presence of 10 mol % of catalyst 1a
in combination with 20 mol % of trifluoroacetic acid, the reaction
proceeded smoothly at 0 °C, affording the desired chiral tertiary
alcohol in 99% yield with excellent enantioselectivity (96% ee, en-
try 1, Table 3). Lowering the temperature resulted in the slight
enhancement of enantio selectivity, but prolonged the reaction
time (see Supplementray data). To our knowledge, this was the
best result attained. Various substituted methyl 2-oxo-2-acetates
reacted with acetone smoothly at 0 °C, and the results are listed
in Table 3. Both electron enriched and deficient substrates can be
tolerated in the system affording excellent yields and enantioselec-
tivities. For example, 4-methoxyphenyl-, 4-methylphenyl-, and
phenyl-substituted esters all gave almost quantitative yields and
96% ee. The pattern of substituents on the aromatic ring seems to
have a slight effect on the enantioselectivities of the reaction. For
example, the 4-methyl phenyl-substituted ester provided higher
enantioselectivity than did the 3-methyl variant (entries 3 and
4). Similarly, methyl 2-oxo-2,40-flurophenyl acetate was reacted
in comparable yield with 94% ee, a much better result than that
of methyl 2-oxo-2,30-flurophenyl acetate (entries 6 and 7). It is
noteworthy that methyl 1-naphthylacetate afforded the product
with 92% ee, a significant increase compared to the literature pro-
cedure11 (entry 8).
Supplementary data
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.tetlet.2008.10.085.
References and notes
1. For reviews of enantioselective organocatalysis see (a) Dalko, P. I.; Moisan, L.
Angew. Chem., Int. Ed. 2001, 40, 3726–3748; (b) Dalko, P. I.; Moisan, L. Angew.
Chem., Int. Ed. 2004, 43, 5138–5175; (c) Taylor, M. S.; Jacobsen, E. N. Angew.
Chem., Int. Ed. 2006, 45, 1520–1543.
2. (a) Marcelli, T.; Maarseveen, J. H. V.; Hiemstra, H. Angew. Chem., Int. Ed. 2006,
45, 7496–7504; (b) Hayashi, Y.; Tamura, T.; Shoji, M. Adv. Synth. Catal. 2004,
346, 1106–1110; (c) Connon, S. J. Chem. Eur. J. 2006, 12, 5418–5427; (d) Erkkilä,
A.; Majander, I.; Pihko, P. Chem. Rev. 2007, 107, 5416–5470; (e) Gaunt, M. J.;
Johansson, C. C. C. Chem. Rev. 2007, 107, 5596–5605.
3. For reviews of chiral nucleophilic chiral amines catalyzed reactions, see: (a)
France, S.; Guerin, D. J.; Lectka, T. Chem. Rev. 2003, 103, 2985–3012; (b) Chen,
Y.; McDaid, P.; Deng, L. Chem. Rev. 2003, 103, 2965–2984; (c) Ouellet, S. G.;
Walji, A. M.; MacMillan, D. W. C. Acc. Chem. Rev. 2007, 40, 1327–1339; (d)
Kizirian, J.-C. Chem. Rev. 2008, 108, 140–205; (e) Atodiresei, I.; Schiffer, I.; Bolm,
C. Chem. Rev. 2007, 107, 5683–5712.
4. (a) Xie, J.-W.; Chen, W.; Li, R.; Zeng, W.; Du, W.; Yue, L.; Chen, Y.-C.; Wu, Y.;
Zhu, J.; Deng, J.-G. Angew. Chem., Int. Ed. 2007, 46, 389–392; (b) Xie, J.-W.; Yue,
L.; Chen, W.; Du, W.; Zhu, J.; Deng, J.-G.; Chen, Y.-C. Org. Lett. 2007, 9, 413–415;
(c) Chen, W.; Du, W.; Yue, L.; Li, R.; Wu, Y.; Ding, L.-S.; Chen, Y.-C. Org. Biomol.
Chem. 2007, 5, 816–821; For the use in asymmetric enamine catalysis with
ketones, see: (d) McCooey, S. H.; Connon, S. J. Org. Lett. 2007, 9, 599–602; (e)
Liu, T.-Y.; Cui, H.-L.; Zhang, Y.; Jiang, K.; Du, W.; He, Z.-Q.; Chen, Y.-C. Org. Lett.
2007, 9, 3671–3674.
In conclusion, a family of novel chiral amines which featured a
tertiary–primary amine structure was synthesized. Their catalytic
performance was demonstrated in asymmetric aldol reactions be-
tween aldehydes or activated ketones and acetone. A variety of
5. Luo, S.-Z.; Xu, H.; Li, J.-Y.; Zhang, L.; Chen, J.-P. J. Am. Chem. Soc. 2007, 129,
3074–3075.
6. Zheng, B.-L.; Liu, Q.-Z.; Guo, C.-S.; Wang, X.-L.; He, L. Org. Biomol. Chem. 2007, 9,
2913–2915.
7. For the representative application of chiral binaphthol in asymmetric
transformation, see: (a) Pu, L. Tetrahedron 2003, 59, 9873–9886; (b) Sasai, H.;
Tokunaga, T.; Watanabe, S.; Suzuki, T.; Itoh, N.; Shibasaki, M. J. Org. Chem. 1995,
60, 7388–7389; (c) Brunel, J. M. Chem. Rev. 2005, 105, 857–898; (d) Pu, L.; Yu,
H.-B. Chem. Rev. 2001, 101, 757–824; (e) Chen, Y.; Yekta, S.; Yudin, A. K. Chem.
Rev. 2003, 103, 3155–3212.
Table 3
Reactions between
a-keto esters and ketones
8. Ooi, T.; Doda, K.; Kameda, M.; Maruoka, K. J. Am. Chem. Soc. 1999, 121, 6159–
6160.
O
O
1a 10 mol%
O
9. The characterization of catalyst 1a: 84%, mp 92–93 °C, ½a D20
ꢀ203.3 (c 0.06 in
ꢁ
OH
MeOOC
R'
R'
COOMe
CHCl3). 1H NMR (300 MHz, CDCl3) 7.93–7.97 (m, 4H), 7.55 (d, J = 8.2 Hz, 2H),
7.43–7.48 (m, 6H), 7.35–7.39 (m, 2H), 7.24–7.29 (m, 3H), 4.36 (dd, J = 10.4,
3.3 Hz, 1H), 3.76 (d, J = 12.2 Hz, 2H), 3.24 (d, J = 12.2 Hz, 2H), 2.76 (dd, J = 12.9,
3.3 Hz, 1H), 2.36 (dd, J = 12.9, 10.8 Hz, 1H), 1.89 (br, 2H) ppm; 13C NMR
(75 MHz, CDCl3) 143.8, 134.9, 133.2, 133.1, 131.3, 128.5, 128.4, 128.2, 127.7,
+
20 mol% TFA
5
7
Entry
R0
R
Yield (%)
7
ee (%)
127.4, 127.3, 126.7, 125.7, 125.4, 62.1, 54.9, 53.6 ppm; IR (film,
m
cmꢀ1): 3431,
2924, 2859, 1628, 1474, 1188, 1039, 837, 746. HRMS (ESI-TOF) calcd for
1
2
3
4
5
6
7
8
C6H5
COOMe
COOMe
COOMe
COOMe
COOMe
COOMe
COOMe
COOMe
99
98
99
99
99
99
99
71
96 (R)a
96
96
90
92
90
94
92
C30H27N2 ([M+H+]) = 415.2174, found 415.2176.
4-MeOC6H5
4-MeC6H5
3-MeC6H5
2-Naphth
3-FC6H5
Compound 1b: >99% yield, mp 124–125 °C, ½a D20
ꢁ
ꢀ103.25 (c 0.4 in CHCl3). 1H
NMR (300 MHz, CDCl3) 8.12 (s, 3H), 7.98–8.02 (m, 7H), 7.56 (t, J = 7.0 Hz, 2H),
7.45 (d, J = 9.0 Hz, 2H), 7.34–7.39 (m, 2H), 7.16–7.18 (m, 3H), 6.75–6.78 (m,
2H), 3.92 (d, J = 12.9 Hz, 2H), 3.23–3.32 (m, 3H), 2.25 (dd, J = 12.9, 3.3 Hz, 1H),
2.03 (dd, J = 12.9, 11.0 Hz, 1H), 1.67 (br, 2H) ppm; 13C NMR (75 MHz, CDCl3)
143.5, 143.4, 137.1, 136.808, 132.5, 132.1, 131.7, 131.3, 130.3, 130.1, 130.0,
128.5, 128.3, 127.4, 127.2, 126.9, 126.7, 126.1, 121.31, 121.26, 121.21, 61.6,
4-FC6H5
1-Naphthyl
53.5, 50.3. IR (film,
m
cmꢀ1): 3390, 2974, 2925, 1597, 1450, 1087, 1050, 758,
Unless otherwise stated, the reaction was carried out with 0.25 mmol of methyl 2-
oxoacetates and 1.0 mL (9.6 mmol) of acetone in the presence of 10 mol % of cata-
lyst 1a in combination with 20 mol % TFA at 0 °C. The enantioselectivities were
determined by chiral AD–H. The absolute configuration of the product is not
determined.
702. HRMS (ESI-TOF) calcd for C46H31F12N2 ([M+H+]) = 839.2296, found
839.2301.
Compound 1c: 94% yield, mp 120–121.5 °C, ½a D20
ꢁ
ꢀ52.5 (c 0.4 in CHCl3). 1H
NMR (300 MHz, CDCl3) 7.95 (m, J = 8.2 Hz, 2H), 7.89 (s, 2H), 7.49–7.55 (m, 2H),
7.40–7.42 (m, 2H), 7.31–7.34 (m, 2H), 7.19–7.29 (m, 7H), 6.92–6.95 (m, 2H),
3.93 (d, J = 12.7 Hz, 2H), 3.55 (dd, J = 10.3, 3.1 Hz, 1H), 3.16 (d, J = 12.8 Hz, 2H),
a
See Refs. 11 and 13c.

Q.-Z. Liu et al. / Tetrahedron Letters 49 (2008) 7434–7437
7437
2.50–3.20 (br, 2H), 2.32 (dd, J = 13.2, 3.1 Hz, 1H), 2.19 (dd, J = 13.2, 10.3 Hz, 1H).
ppm; 13C NMR (75 MHz, CDCl3) 152.7, 152.6, 149.4, 149.33, 149.25, 149.2,
137.3, 137.22, 137.16, 136.6, 132.4, 131.0, 130.4, 129.6, 128.41, 128.39, 127.6,
keto esters). The mixture was directly purified through flash column
chromatography on a silica gel (n-hexane/ethyl acetate = 8/1–2/1) to give the
pure adduct affording the desired adducts.
127.4, 126.7, 126.6, 126.5, 114.3, 114.0, 60.6, 53.9, 50.4 ppm; IR (film,
m
cmꢀ1):
11. (a) Wang, F.; Xiong, Y.; Liu, X.; Feng, X. Adv. Synth. Catal. 2007, 349, 2665–2668;
(b) Liu, J.; Yang, Z.; Wang, Z.; Wang, F.; Chen, X.; Liu, X.; Feng, X.; Su, Z.; Hu, C. J.
Am. Chem. Soc. 2008, 130, 5654–5655.
12. (a) Grover, P. T.; Bhongle, N. N.; Wald, S. A.; Senanayake, C. H. J. Org. Chem.
2000, 65, 6283–6287; (b) Masumoto, S.; Suzuki, M.; Kanai, M.; Shibasaki, M.
Tetrahedron Lett. 2002, 43, 8647–8651; (c) Senanayake, C. H.; Fang, K.; Grover,
P.; Bakale, R. P.; Vandenbossche, C. P.; Wald, S. A. Tetrahedron Lett. 1999, 40,
819–822; (d) Masumoto, S.; Suzuki, M.; Kanai, M.; Shibasaki, M. Tetrahedron
2004, 60, 10497–10504; (e) Gupta, P.; Fernandes, R. A.; Kumar, P. Tetrahedron
Lett. 2003, 44, 4231–4232.
13. (a) Bogevig, A.; Kumaragurubaran, N.; Jøgensen, K. A. Chem. Commun. 2002,
620–621; (b) Tokuda, O.; Kano, T.; Gao, W. G.; Ikemolo, I.; Maruoka, K. Org. Lett.
2005, 7, 5103–5105; (c) Tang, Z.; Cun, L.-F.; Cui, X.; Mi, A.-Q.; Jiang, Y.-Z.; Gong,
L.-Z. Org. Lett. 2006, 8, 1263–1266; (d) Mase, N.; Tanaka, F.; Barbas, C. F., III
Angew. Chem., Int. Ed. 2004, 43, 2420–2423; (e) Wang, W.; Li, H.; Wang, J.
Tetrahedron Lett. 2005, 46, 5077–5079.
3429, 2923, 1614, 1527, 1447, 1241, 1045, 750, 703. HRMS (ESI-TOF) calcd for
C42H29F6N2 ([M+H+]) = 675.2234, found 675.2207.
Compound 1d: 82% yield, mp 112.5–113 °C, ½a D20
ꢁ
ꢀ18.75 (c 0.4 in CHCl3). 1H
NMR (300 MHz, CDCl3) 7.94–7.97 (m, 4H), 7.62 (d, J = 6.4 Hz, 4H), 7.43–7.53 (m,
10H), 7.26–7.31 (m, 2H), 7.16–7.22 (m, 3H), 6.83–6.86 (m, 2H), 4.04 (d,
J = 12.5 Hz, 2H), 3.33 (dd, J = 10.5, 3.0 Hz, 1H), 3.21 (d, J = 12.5 Hz, 2H), 2.34 (dd,
J = 12.8, 3.0 Hz, 1H), 2.06 (br, 2H), 1.95 (dd, J = 12.8, 10.5 Hz, 1H) ppm; 13C NMR
(75 MHz, CDCl3) 141.4, 140.2, 136.4, 132.5, 131.2, 130.7, 130.0, 129.4, 128.7,
128.4, 128.2, 128.1, 127.5, 127.2, 127.1, 125.9, 125.8, 60.6, 53.2, 50.1 ppm; IR
(film,
m
cmꢀ1): 3390, 2973, 2925, 1489, 1449, 1087, 1050, 885, 758, 702. HRMS
(ESI-TOF) calcd for C42H35N2 ([M+H+]) = 567.2800, found 567.2802.
10. General procedure for the direct aldol reactions: A mixture of anhydrous acetone
(1.0 mL), aromatic aldehydes or
(10.4 mg, 0.025 mmol, 10 mol%) TFA (3.7
at ambient temperature for 32–41 h (aldehydes) or at 0 °C for 34–168 h (
a
-keto esters (0.25 mmol), catalyst 1a
l
L, 0.05 mmol, 20 mol%) was stirred
a-