Highly enantioselective organocatalyzed construction of quaternary carbon centers via cross-aldol reaction of ketones in water

Article abstract of DOI:10.1002/adsc.200800248

The asymmetric construction of quaternary carbon centers via cross-aldol reactions of ketones with β,γ-unsaturated keto esters catalyzed by 4-(tert-butyldiphenylsilyloxy)-pyrrolidine-2-carboxylic acid in water is described. The adducts bearing two adjacen

Full text of DOI:10.1002/adsc.200800248

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DOI: 10.1002/adsc.200800248
Highly Enantioselective Organocatalyzed Construction of
Quaternary Carbon Centers via Cross-Aldol Reaction of
Ketones in Water
Changwu Zheng,a Yongyong Wu,a Xiaosheng Wang,a and Gang Zhaoa,*
a
Laboratory of Modern Organic Synthetic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of
Sciences, 354 Fenglin Lu, Shanghai, 200032, Peopleꢀs Republic of China
Fax : (+86)-21-6416-6128; e-mail: zhaog@mail.sioc.ac.cn
Received: April 25, 2008; Revised: September 28, 2008; Published online: November 19, 2008
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/adsc.200800248.
Abstract: The asymmetric construction of quaterna-
ry carbon centers via cross-aldol reactions of ke-
tones with b,g-unsaturated keto esters catalyzed by
4-(tert-butyldiphenylsilyloxy)-pyrrolidine-2-carbox-
ylic acid in water is described. The adducts bearing
two adjacent chiral centers were obtained in high
yields, mostly up to 99% ee, and with high diaste-
reoselectivities. The corresponding polyfunctional
products could also be easily transformed to useful
lactones with three chiral centers.
catalytic asymmetric intermolecular aldol reactions of
the ketone-ketone type are less well developed.[9]
a-Keto esters behaving as activated ketones have
been used in a great deal of reactions.[10] The addition
to the a-carbonyl group of these compounds creates a
quaternary center. Just recently, the asymmetric direct
aldol reactions between cyclohexanone and phenyl-
glyoxylates have been reported by Maruoka,[9a] Cꢁr-
dova[9b] and Zhao.[9c] Other intermolecular aldol reac-
tions of ketones using acetone as the nucleophile and
trifluromethylated ketones as the electrophile[11] have
also been reported by Gong,[11a] Zhao[11b] and Liu[12]
et al. However, most of the reactions of cyclohexa-
none reported above, especially those using the a-
keto esters as the electrophile, suffered from several
drawbacks such as high catalyst loading, a large
excess of nucleophilic ketones and long reaction
Keywords: aldols; ketones; organocatalysis; quater-
nary stereocenters; water
The development of new carbon-carbon bond forma- time.[9a,b] Herein, we would like to report a highly ste-
tion reactions has been one of the most challenging reoselective cross-aldol reaction of ketones to b,g-un-
problems in organic synthesis,[1] especially in the con- saturated keto esters catalyzed by proline derivatives
text of creating new quaternary carbon centers with in water.
high enantio- and diastereoselectivity involving a cat-
Initially, the reaction of a-keto ester 1a with cyclo-
alyzed asymmetric reaction. Quaternary carbon cen- hexanone was examined in the presence of l-proline
ters are prevalent throughout most classes of natural 3a and other proline-derived catalysts shown in
products and pharmaceutical agents;[2] hence, there Scheme 1. The results are compiled in Table 1. The
are numerous ingenious methods that have been de- addition of cyclohexanone to 1a catalyzed by 3a in
veloped to selectively access this structural motif.[3] neat cyclohexanone gave the tertiary alcohol 2a in
Despite these advances, the solution to this far-reach- moderate yield and enantioselectivity at room tem-
ing problem has not been completely attained. On the perature (entry 1 in Table 1). A similar result was ob-
other hand, asymmetric organocatalysis is a rapidly tained when the catalyst cis-siloxy-d-proline 5 was
growing and important field of organic chemistry.[4] used (entry 6 in Table 1). Gratifyingly, a change of the
Especially, the proline-catalyzed aldol reaction plays configuration of 5 led to an improved result, the
an important role in carbon-carbon bond formation trans-siloxy-l-proline 3c was capable of furnishing 2a
reactions.[5] The intermolecular aldol reactions of the in good yield and advanced selectivity after 48 h.
ketone-aldehyde type and aldehyde-aldehyde type (entry 3 in Table 1). This improvement can be ex-
with mostly high stereoselectivities have been report- plained by referring to the transition state, the cis-
ed by List,[6] Barbas[7] and Hayashi[8] et al. In contrast, TBDPS substitution in the catalyst 5 disturbs the H-
bonding interaction of the carboxyl group with the
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Adv. Synth. Catal. 2008, 350, 2690 – 2694

Highly Enantioselective Organocatalyzed Construction of Quaternary Carbon Centers
COMMUNICATIONS
Table 2. The effect of solvents and catalyst loadings on the
yield and selectivity.[a]
Entry Solvent
t [h] Yield [%][b] ee [%][c] dr[d]
1
2
3
4
5
6
DMF
CHCl3
Toluene 48
i-PrOH
EtOH
MeOH
H2O
H2O
H2O
48
48
55
52
62
55
45
64
83
83
76
69
52
78
84
96
88
77
85
98
97
99
98
99
24:1
1:1
>19:1
7:3
19:1
24
24
24
24
24
24
24
24
19:1
7[e]
8[e,f]
9[e,g]
10[e,h]
11[e,g,i]
>19:1
>19:1
>19:1
>19:1
>19:1
Scheme 1. Organocatalysts tested in this study.
H2O
H2O
[a]
Table 1. The effect of catalysts on the reaction yield and se-
Unless otherwise specified, the reaction was carried out
with 1a (0.1 mmol) and cyclohexanone (0.5 mmol) in the
solvent (0.5 mL) in the presence of catalysts 3c (30
mol%) at room temperature.
lectivity.[a]
[b]
[c]
[d]
Yields of isolated products.
Determined by chiral HPLC.
1
Determined by H NMR spectroscopy of the crude prod-
ucts or HPLC.
1.0 mL of water was used.
20 mol% of the catalyst was loaded.
15 mol% of the catalyst was loaded.
10 mol% of the catalyst was loaded.
0.3 mmol of cyclohexanone was employed
[e]
[f]
[g]
[h]
[i]
Entry
Catalyst
t [h]
Yield [%][b]
ee [%][c]
dr[d]
1
2
3
4
5
6
7
3a
3b
3c
3d
4
5
6
48
72
48
72
72
48
72
72
<5
86
<10
<10
62
55
–
82
–
19:1
–
24:1
–
–
19:1
–
–
À50
completed in a short time although with some decline
in yield and diastereoselectivity compared to that in
neat cyclohexanone (entries 4–6 in Table 2). Water as
the solvent was also investigated. When the reaction
was carried out in water, good yield and nearly a
single isomer were obtained[13](entry 7 in Table 2). In
comparison, the reaction proceeded in non-protonic
solvents to give 2a with a low yield and moderate dia-
stereoselectivity, except for toluene as the solvent (en-
tries 1–3 in Table 2).
<5
–
[a]
Unless otherwise noted, the reaction was carried out
with 1a (0.1 mmol) in cyclohexanone (0.5 mL) in the
presence of catalysts (30 mol%) at room temperature.
Yield of isolated product.
Determined by chiral HPLC.
Determined by H NMR spectroscopy of the crude prod-
[b]
[c]
[d]
1
ucts and HPLC analysis.
substrate and therefore is inferior to 3c. Other cata-
A further study was carried out with different cata-
lysts potentially suitable for aldol reactions seemed to lyst loadings and amounts of cyclohexanone in water.
be inactive to this ketone-to-ketone reactions. The Decreasing the amount of the catalyst 3c from 30%
same reaction catalyzed by other substituted prolines to 10% led to a slight change in yield and enantiose-
or prolinamide afforded only trace of the adduct 2a lectivity (entries 7–10 in Table 2). But a great loss of
(entries 2, 4, 5 and 7, in Table 1). The effect of the sil- yield was observed when cychexanone was reduced
ACHTUNGTRENNUNG
ACHTUNGTRENNUNG
the catalysts. Introduction of the hydrophobic siloxy above, the compatibility of 3c with a-keto esters
moiety into the catalyst creates a hydrophobic organic having various steric and electronic characteristics
phase in the presence of water, which is most proba- was then investigated in water. The results are shown
bly the key to the excellent reactivity and stereoselec- in Table 3.
tivity[8f]
.
Generally, excellent enantio- and diastereoselectivi-
Next, the effects of solvents on the yield and selec- ties could be achieved with b,g-unsaturated a-keto
tivity of this reaction were also investigated. The re- esters bearing various segments of esters or g-aryl
sults were summarized in Table 2. Protonic solvents substituents in 24 h. All of the reactions gave the
seemed to be advantageous for this reaction. When aldol adducts in up to 99% ee and the values of the
isopropyl alcohol, as well as ethanol and methanol, diastereoselectivities were also up to 19:1. The yields
was employed as the solvent, the reaction could be of the products ranged from moderate to high de-
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Changwu Zheng et al.
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Table 3. Scope of the cross-aldol reaction of 1 to yield the
tertiary alcohol 2.[a]
Table 4. Cross-aldol reaction of 1b with acetone and other
cyclic ketones.[a]
Entry Ar, R
t [h] Prod
G
dr[d]
Entry R1, R2
Product Yield
[%][b]
ee
dr[d]
[%][c]
1
2
3
4
5
6
Ph, Me
Ph, Et
24
18
18
18
24
18
18
2a
2b
2c
2d
2e
2f
2g
2h
2i
2i
2j
2k
2m
2n
76
99
99
98
77
85
99
74
77
67
74
92
80
72
99
>19:1
1[e]
2
3
4
5
H, H
2o
2p
2q
2r
85
41
53
50
56
45
93
93
86
81
-
>99 >19:1
>99 >19:1
>99 >19:1
>99 >19:1
>99 >19:1
>99 >19:1
>99 >19:1
>99 >19:1
-CH2CH2-
-CH2OCH2-
-CH2SCH2-
-CH2N-
19:1
19:1
24:1
19:1
Ph, Allyl
Ph, i-Pr
Ph, Benzyl
Ph, t-Bu
p-FC6H4, Me
p-ClC6H4, Me 24
p-BrC6H4, Me 24
p-BrC6H4, Me 24
m-ClC6H4, Me 24
o-BrC6H4, Me 24
p-MeC6H4, Me 24
2s
AHCTUNGTERN(GNUN Boc)CH2-
7
8[f]
9
[a]
Unless otherwise specified, the reaction of 1b (0.1 mmol)
with acetone or other cyclic ketones (10 equiv.) in water
(1.0 mL) was carried out in the presence of catalysts 3c
(15 mol%) at room temperature for 48 h.
Yield of isolated product.
10[e]
11[f]
12
13[f]
14
98
>19:1
>99 19:1
[b]
[c]
[d]
>99 >19:1
>99 >19:1
>99 >24:1
Determined by chiral HPLC.
Determined by H NMR spectroscopy of the crude prod-
1
2-Furyl, Me
24
ucts and HPLC analysis.
5 equivalents of cyclohexanone were used and the reac-
tion was stirred for 24 h.
[a]
Unless otherwise specified, the reaction of 1 (0.1 mmol)
with cyclohexanone (5 equiv.) in water (1.0 mL) was car-
ried out in the presence of catalysts 3c (15 mol%) at
room temperature.
[e]
[b]
[c]
[d]
Yield of isolated product.
phatic ketones such as 2-butanone, 3-methyl-2-buta-
none, hydroxyacetone, dihydroxyacetone and 1-(tert-
butyldimethylsilyloxy)propan-2-one were also studied,
but no desired products were obtained with the start-
ing materials being recovered. It should also be noted
that no Michael products or hemiketals were detected
in the reactions through 1H NMR analysis of the
Determined by chiral HPLC.
1
Determined by H NMR spectroscopy of the crude prod-
ucts and HPLC analysis.
The reaction was carried out on 1.0 mmol scale.
10 equivalents of cyclohexanone were used.
[e]
[f]
pending on the solubility of the substrates in the two- crude products.
phase system. Substrates with good solubility afforded
The adduct of the aldol reaction 2i may be easily
the desired products with yields from 85% to 99% in converted to a bicyclic lactone 7 through a simple re-
short times (entries 2–4, 6, 7 and 12 in Table 3). Those duction and subsequent acid treatment.[11a] The prod-
with lower solubility gave the products in moderate uct containing two adjacent chiral centers and a qua-
yields (entries 1 and 5 in Table 3). Additionally, more ternary carbon was obtained with a 10:1 diastereose-
cyclohexanone was needed to obtain high yields in lectivity[14] (Sheme 2).
short times when the substrates had a poor solubility
The absolute configuration of the tertiary alcohol 2
in the system (entries 8, 11 and 13 in Table 3). None- was assigned by X-ray structural analysis of 2i to be
theless, the product 2i may be obtained with almost 2S,3R.[15] The absolute configuration observed may be
no loss of stereoselectivity even when the reaction explained by an intermolecular version of a hydro-
was scaled up 10 times (entry 10 in Table 3).
gen-bond activation and then attack of the carbonyl
Changing cyclohexanone to acetone or other rela- group from back as shown in Figure 1. Hindrance be-
tively inactive ketones resulted in a decrease in yields tween the tert-butyldiphenylsilyloxy group and the
and selectivities. The addition of acetone to 1b afford-
ed the adduct 3o with 45% ee in good yield (entry 1
in Table 4), while cyclopentanone and other heterocy-
clic ketones gave the corresponding products only in
moderate yields ranging from 41% to 56%, which was
attributed to their low reaction activities. The ee
values of the products 3p–3s ranged from 81% to
93%, accompanied by a slight decrease in diastereose-
lectivities (entries 2–5 in Table 4). Other acyclic ali- Scheme 2. Conversion of 2i to 7
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Highly Enantioselective Organocatalyzed Construction of Quaternary Carbon Centers
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Acknowledgements
The generous financial support from the National Natural
Science Foundation of China (No. 20172064, 203900502,
20532040), QT Program, Shanghai Natural Science Council,
and Excellent Young Scholars Foundation of National Natu-
ral Science Foundation of China (20525208) are gratefully ac-
knowledged.
References
[1] For reviews see: a) B. L. Feringa, Acc. Chem. Res. 2000,
33, 346; b) R. Ballini, G. Bosica, D. Fiorini, A. Pal-
mieri, M. Petrini, Chem. Rev. 2005, 105, 933; c) S. B.
Tsogoeva, Eur. J. Org. Chem. 2007, 1701.
[2] For reviews, see a) K. Fuji, Chem. Rev. 1993, 93, 2037;
b) E. J. Corey, A. Guzman-Perez, Angew. Chem. 1998,
110, 402; Angew. Chem. Int. Ed. 1998, 37, 388; c) J.
Christoffers, A. Mann, Angew. Chem. 2001, 113, 4725;
Angew. Chem. Int. Ed. 2001, 40, 4591.
Figure 1. X-ray structure of adduct 2i and the proposed tran-
sition state.
[3] a) J. C. Ruble, G. C. Fu, J. Am. Chem. Soc. 1998, 120,
11532; b) M. Chavarot, J. J. Byrne, P. Y. Chavant, Y.
Vallee, Tetrahedron: Asymmetry 2001, 12, 1147; c) P.
Vachal, E. N. Jacobsen, J. Am. Chem. Soc. 2002, 124,
10012; d) S. Masumoto, H. Usuda, M. Suzuki, M.
Kanai, M. Shibasaki, J. Am. Chem. Soc. 2003, 125,
5634; e) S. A. Shaw, P. Aleman, E. Vedejs, J. Am.
Chem. Soc. 2003, 125, 13368; f) X. Liu, H. Li, L. Deng,
Org. Lett. 2005, 7, 167; g) D. Ikeda, M. Kawatsura, J.
Uenishi, Tetrahedron Lett. 2005, 46, 6663; h) R. Wada,
T. Shibuguchi, S. Makino, K. Oisaki, M. Kanai, M. Shi-
basaki, J. Am. Chem. Soc. 2006, 128, 7687; i) H.
Miyabe, Y. Yamaoka, Y. Takemoto, J. Org. Chem.
2006, 71, 2099; j) Y.-X. Jia, J. Zhong, S.-F. Zhu, C.-M.
Zhang, Q.-L. Zhou, Angew. Chem. Int. Ed. 2007, 46,
5565; k) S. Arns, M. E. Lebrun, C. M. Grise, I. Denisso-
va, L. Barriault, J. Org. Chem. 2007, 72, 9314; l) S. A.
Babu, M. Yasuda, A. Baba, J. Org. Chem. 2007, 72,
10264; m) K. M. Bogle, D. J. Hirst, D. J. Dixon, Org.
Let. 2007, 9, 4901; n) B. Castagner, J. L. Leighton, Tet-
rahedron 2007, 63, 5895; o) D. Enders, O. Niemeier, L.
Straver, Synlett 2006, 3399.
[4] a) A. Berkessel, H. Grçger, Asymmetric Organocataly-
sis: From Biomimetic Concepts to Applications in
Asymmetric Synthesis Wiley-VCH, Weinheim, 2004;
b) P. I. Dalko, L. Moisan, Angew. Chem. Int. Ed. 2001,
40, 3726; c) P. I. Dalko, L. Moisan, Angew. Chem. Int.
Ed. 2004, 43, 5138; d) J. Seayad, B. List, Org. Biomol.
Chem. 2005, 3, 719; e) H. Pellissier, Tetrahedron 2007,
63, 9267; f) S. Mukherjee, J. W. Yang, S. Hoffmann, B.
List, Chem. Rev. 2007, 107, 5471.
aryl section of the keto esters may be responsible for
the excellent enatioselectivities and diastereoselectivi-
ties.
In conclusion, the present report reveals a highly
efficient organocatalyzed cross-aldol reaction of ke-
tones with b,g-unsaturated a-keto esters in the pres-
ence of water that provides a simple and direct access
to the corresponding tertiary aldol products in excel-
lent enantioselectivities and high diastereoselectivi-
ties. The protocol is practical and quite efficient. Fur-
ther applications of these reactions are currently
under investigation.
Experimental Section
Typical Procedure for the Cross-Aldol Reaction using
Catalyst 3c in Water
The following procedure for the reaction of methyl 2-oxo-4-
phenylbut-(E)-3-enoate (1a) with cyclohexanone in water
using catalyst 3c is representative. To a mixture of catalyst
3c (6.0 mg, 0.015 mmol), and methyl 2-oxo-4-phenylbut-(E)-
3-enoate (1a) (19 mg, 0.1 mmol) in water (1.0 mL), cyclo-
hexanone (52 mL, 0.5 mmol) was added at room tempera-
ture. The reaction mixture was vigorously stirred for the
time indicated in the tables, then extracted with ethyl ace-
tate (3ꢃ3 mL), and dried over Na2SO4. Purification by flash
chromatography (hexane/EtOAc, 10:1–5:1) afforded prod-
uct 2a as a yellow oil; yield: 76%; [a]2D4:3: À110.9 (c 1.15,
[5] a) B. List, R. A. Lerner, C. F. Barbas III, J. Am. Chem.
Soc. 2000, 122, 2395; b) B. List, P. Pojarliev, C. Castello,
Org. Lett. 2001, 3, 573; c) K. Sakthivel, W. Notz, T. Bui,
C. F. Barbas III, J. Am. Chem. Soc. 2001, 123, 5260;
d) S. Chandrasekhar, C. Narsihmulu, N. R. Reddy, S. S.
Sultana, Chem. Commun. 2004, 2450; e) M. Edin, J.-E.
Bꢄckvall, A. Cꢁrdova, Tetrahedron Lett. 2004, 45, 7697;
1
CHCl3); H NMR (300 MHz, CDCl3): d=7.31 (m, 5H), 6.90
(d, J=15.8 Hz, 1H), 6.04 (d, J=15.9 Hz, 1H), 3.77 (s, 3H),
3.63 (s, 1H), 3.13 (m, 1H), 2.04 (m, 2H), 2.11 (m, 2H), 1.94
(m, 1H), 1.68 (m, 3H); IR (neat): n=3519, 2948, 1737, 1708,
1245, 1147, 976 cmÀ1; HPLC separation conditions: Chiralcel
˙
f) J. Casas, H. Sunden, A. Cꢁrdova, Tetrahedron Lett.
AS-H, 208C, 254 nm, 90:10 hexane/i-PrOH, 1.0 mLminÀ1
;
2004, 45, 6117; g) K. Funabiki, H. Yamamoto, H.
Nagaya, M. Matsui, Tetrahedron Lett. 2006, 47, 5507;
t
major =26.1 min, tminor =16.4 min.
Adv. Synth. Catal. 2008, 350, 2690 – 2694
ꢂ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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2693

Changwu Zheng et al.
COMMUNICATIONS
h) A. M. Bernard, A. Frongia, R. Guillot, P. P. Piras, F.
Secci, M. Spiga, Org. Lett. 2007, 9, 541; i) A. B. Northr-
up, D. W. C. MacMillan, J. Am. Chem. Soc. 2002, 124,
6798; j) R. I. Storer, D. W. C. MacMillan, Tetrahedron
2004, 60, 7705; k) G.-L. Zhao, W.-W. Liao, A. Cꢁrdova,
Tetrahedron Lett. 2006, 47, 4929; l) A. B. Northrup,
I. K. Mangion, F. Hettche, D. W. C. MacMillan, Angew.
Chem. Int. Ed. 2004, 43, 2152.
h) M. Guo, D. Li, Y. Sun, Z. G. Zhang, Synlett 2004,
741; i) F. Gohier, K. Bouhadjera, D. Faye, C. Gaulon,
V. Maisonneuve, G. Dujardin, R. Dhal, Org. Lett. 2007,
9, 211; j) H. L. van Lingen, W. Zhuang, T. Hansen,
F. P. J. T. Rutjes, K. A. Jørgensen, Org. Biomol. Chem.
2003, 1, 1953; k) N. Halland, T. Velgaard, K. A. Jørgen-
sen, J. Org. Chem. 2003, 68, 5067; l) C.-L. Cao, X.-L.
Sun, Y.-B. Kang, Y. Tang, Org. Lett. 2007, 9, 4151; m) S.
Samanta, J. Krause, T. Mandal, C.-G. Zhao, Org. Lett.
2007, 9, 2745.
[6] a) S. Bahmanyar, K. N. Houk, H. J. Martin, B. List, J.
Am. Chem. Soc. 2003, 125, 2475; b) L. Hoang, S. Bah-
manyar, K. N. Houk, B. List, J. Am. Chem. Soc. 2003,
125, 16; c) B. List, Tetrahedron 2002, 58, 5573; d) B.
List, J. Am. Chem. Soc. 2000, 122, 9336; e) B. List,
R. A. Lerner, C. F. Barbas III, J. Am. Chem. Soc. 2000,
122, 2395; f) W. Notz, B. List, J. Am. Chem. Soc. 2000,
122, 7386; g) B. List, R. A. Lerner, C. F. Barbas III,
Org. Lett. 1999, 1, 59.
[7] a) N. Mase, F. Tanaka, C. F. Barbas III, Org. Lett. 2003,
5, 4369; b) R. Thayumanavan, F. Tanaka, C. F. Barbas
III, Org. Lett. 2004, 6, 3541; c) N. Utsumi, M. Imai, F.
Tanaka, S. S. V. Ramasastry, C. F. Barbas III, Org. Lett.
2007, 9, 3445; d) G. F. Zhong, J. H. Fan, C. F. Barbas
III, Tetrahedron Lett. 2004, 45, 5681.
[8] a) S. Aratake, T. Itoh, T. Okano, N. Nagae, T. Sumiya,
M. Shoji, Y. Hayashi, Chem. Eur. J. 2007, 13, 10246;
b) S. Aratake, T. Itoh, T. Okano, T. Usui, M. Shoji, Y.
Hayashi, Chem. Commun. 2007, 2524; c) Y. Hayashi, S.
Aratake, T. Itoh, T. Okano, T. Sumiya, M. Shoji, Chem.
Commun. 2007, 957; d) Y. Hayashi, S. Aratake, T.
Okano, J. Takahashi, T. Sumiya, M. Shoji, Angew.
Chem. Int. Ed. 2006, 45, 5527; e) Y. Hayashi, H. Sekiza-
wa, J. Yamaguchi, H. Gotoh, J. Org. Chem. 2007, 72,
6493; f) Y. Hayashi, T. Sumiya, J. Takahashi, H. Gotoh,
T. Urushima, M. Shoji, Angew. Chem. Int. Ed. 2006, 45,
958; g) Y. Hayashi, T. Urushima, M. Shoji, T. Uchi-
maru, I. Shiina, Adv. Synth. Catal. 2005, 347, 1595.
[9] a) O. Tokuda, T. Kano, W.-G. Gao, T. Ikemoto, K. Mar-
uoka, Org. Lett. 2005, 7, 5103; b) A. Cꢁrdova, W. B.
Zou, P. Dziedzic, I. Ibrahem, E. Reyes, Y. Xu, Chem.
Eur. J. 2006, 12, 5383; c) R. Dodda, C.-G. Zhao, 2007,
Synlett 1605; d) K. Mikami, Y. Kawakami, K. Akiyama,
K. Aikawa, J. Am. Chem. Soc. 2007, 129, 12950;
e) D. A. Evans, M. C. Kozlowski, C. S. Burgey, D. W. C.
MacMillan, J. Am. Chem. Soc. 1997, 129, 7893.
[11] a) X. Y. Xu, Z. Tang, Y. Z. Wang, S. W. Luo, L. F. Cun,
L. Z. Gong, J. Org. Chem. 2007, 72, 9905; b) S. Saman-
ta, C.-G. Zhao, J. Am. Chem. Soc. 2006, 128, 7442; c) F.
Wang, Y. Xiong, X. Liu, X. Feng, Adv. Synth. Catal.
2007, 349, 2665.
[12] a) X. J. Wang, Y. Zhao, J. T. Liu, Org. Lett. 2002, 9,
1343; b) Y. Zhao, X. J. Wang, J. T. Liu, Synlett 2008,
1017.
[13] For selected aldol reactions carried out in water see:
a) Y. Y. Wu, Y. Z. Zhang, M. L. Yu, G. Zhao, S. W.
Wang, Org. Lett. 2006, 8, 4417; b) M. Amedjkouh, Tet-
rahedron: Asymmetry 2005, 16, 1411; c) S. S. Chimni,
D. Mahajan, Tetrahedron: Asymmetry 2006, 17, 2108;
d) P. Dziedzic, W. B. Zou, J. Hafren, A. Cordova, Org.
Biomol. Chem. 2006, 4, 38; e) M. Gruttadauria, F. Giac-
alone, A. M. Marculescu, P. Lo Meo, S. Riela, R. Noto,
Eur. J. Org. Chem. 2007, 4688; f) D. Gryko, W. J. Sale-
tra, Org. Biomol. Chem. 2007, 5, 2148; g) S. Guizzetti,
M. Benaglia, L. Raimondi, G. Celentano, Org. Lett.
2007, 9, 1247; h) J. Huang, X. Zhang, D. W. Armstrong,
Angew. Chem. Int. Ed. 2007, 46, 9073; i) M. Lei, L. X.
Shi, G. Li, S. Chen, W. H. Fang, Z. M. Ge, T. M. Cheng,
R. T. Li, Tetrahedron 2007, 63, 7892; j) Y. X. Liu, Y. N.
Sun, H. H. Tan, W. Liu, J. C. Tao, Tetrahedron: Asym-
metry 2007, 18, 2649; k) Y. X. Liu, Y. N. Sun, H. H.
Tan, J. C. Tao, Catal. Lett. 2008, 120, 281; l) S. Z. Luo,
J. Y. Li, L. Zhang, H. Xu, J. P. Cheng, Chem. Eur. J.
2008, 14, 1273; m) V. Maya, M. Raj, V. K. Singh, Org.
Lett. 2007, 9, 2593; n) A. I. Nyberg, A. Usano, P. M.
Pihko, Synlett 2004, 1891; o) Y. Orito, S. Hashimoto, T.
Ishizuka, M. Nakajima, Tetrahedron 2006, 62, 390;
p) Y. C. Teo, Tetrahedron: Asymmetry 2007, 18, 1155;
q) X. Y. Wu, Z. Q. Jiang, H. M. Shen, Y. X. Lu, Adv.
Synth. Catal. 2007, 349, 812.
[10] a) T. Akiyama, S. Funaki, K. Fuchibe, Heterocycles
2006, 67, 369; b) B. Jiang, Z. L. Chen, X. X. Tang, Org.
Lett. 2002, 4, 3451; c) W. Seufert, A. Fleury, B. Giese,
Synlett 2006, 1774; d) J. Vabeno, M. Brisander, T.
Lejon, K. Luthman, J. Org. Chem. 2002, 67, 9186; e) K.
Juhl, K. A. Jøgensen, Angew. Chem. Int. Ed. 2003, 42,
1498; f) D. A. Evans, J. S. Johnson, E. J. Olhava, J. Am.
Chem. Soc. 2000, 122, 1635; g) Y.-C. Wu, L. Liu, H.-J.
Li, D. Wang, Y.-J. Chen, J. Org. Chem. 2006, 71, 6592;
[14] The absolute configuration of the major product was
assigned by NOE analysis.
[15] CCDC 686242 [for 2i, Formula: C17H19BrO4, unit cell
parameters:
a=5.6130(7),
b=10.7903(14),
c=
27.566(4), space group P212121] contains the supple-
mentary crystallographic data for this paper. These
data can be obtained free of charge from The Cam-
bridge Crystallographic Data Centre via www.ccdc.ca-
m.ac.uk/data_request/cif.
2694
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Adv. Synth. Catal. 2008, 350, 2690 – 2694