Highly efficient and reusable dendritic catalysts derived from N-prolylsulfonamide for the asymmetric direct aldol reaction in water

Article abstract of DOI:10.1021/ol061418q

The direct aldol reactions catalyzed by chiral dendritic catalysts derived from N-prolylsulfonamide gave the corresponding products in high isolated yields (up to 99%) with excellent anti diastereoselectivities (up to >99:1) and enantioselectivities (up t

Full text of DOI:10.1021/ol061418q

ORGANIC
LETTERS
2006
Vol. 8, No. 20
4417-4420
Highly Efficient and Reusable Dendritic
Catalysts Derived from
N-Prolylsulfonamide for the Asymmetric
Direct Aldol Reaction in Water
Yongyong Wu,† Yazhu Zhang,‡ Menglong Yu,‡ Gang Zhao,*,‡ and Shaowu Wang*,†
Anhui Key Laboratory of Functional Molecular Solids, Institute of Organic Chemistry,
School of Chemistry and Materials Science, Anhui Normal UniVersity, Wuhu, Anhui
241000, China, and Laboratory of Medern Synthetic Organic Chemistry, Shanghai
Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032, China
zhaog@mail.sioc.ac.cn; swwang@mail.ahnu.edu.cn
Received June 10, 2006
ABSTRACT
The direct aldol reactions catalyzed by chiral dendritic catalysts derived from N-prolylsulfonamide gave the corresponding products in high
isolated yields (up to 99%) with excellent anti diastereoselectivities (up to >99:1) and enantioselectivities (up to >99% ee) in water. In addition,
catalyst 1e may be recovered by precipitation and filtration and reused for at least five times without loss of catalytic activity.
The aldol reaction is recognized as one of the most powerful
carbon-carbon bond-forming reactions in modern organic
synthesis.1 The great synthetic usefulness of the catalytic
asymmetric aldol reaction has powered a rapid evolution of
numerous highly enantioselective chiral catalysts, and in
recent years, more attention has been paid to developing
organocatalysts for the asymmetric direct aldol reactions.2
Because water is safe, economical, and environmentally
benign, it has been employed in catalytic asymmetric reac-
tions as a substitute for conventional organic solvents.3 The
development of catalytic asymmetric direct aldol reactions
in aqueous organic solvents has been explored by using metal
complexes.4 Although organocatalysts (such as proline and
several chiral diamines) showed the catalytic activity for the
direct aldol additions in buffered aqueous media, the observ-
ed diastereo- and enantioselectivities are still disappointing.2h,5
In contrast, the biochemical aldol reactions catalyzed by the
aldolases and antibodies occur perfectly in aqueous media.6
The use of aldolases and antibodies, however, has been
(2) For reviews, see: (a) Carreira, E. M. Mukaiyama Aldol Reaction. In
ComprehensiVe Asymmetric Catalysis; Jacobsen, E. N., Pfaltz, A., Yama-
moto, H., Eds.; Springer-Verlag: Heidelberg, 1999; Vol. III, Chapter 29.1.
(b) Mahrwald, R. Chem. ReV. 1999, 99, 1095. (c) Johnson, J. S.; Evans, D.
A. Acc. Chem. Res. 2000, 33, 325. (d) Machajewski, T. D.; Wong, C.-H.
Angew. Chem., Int. Ed. 2000, 39, 1352. (e) List, B.; Pojarliev, P.; Castello,
C. Org. Lett. 2001, 3, 573. (f) Bogevig, A.; Kumaragurubaran N.; Jorgensen,
K. A. Chem. Commun. 2002, 620. (g) Cordova, A.; Notz, W.; Barbas, C.
F., III. Chem. Commun. 2002, 3024. (h) Bahmanyar, S.; Houk, K. N.; Martin,
H. J.; List, B. J. Am. Chem. Soc. 2003, 125, 2475. (i) Hoang, L.; Bahmanyar,
S.; Houk, K. N.; List, B. J. Am. Chem. Soc. 2003, 125, 16. (j) Kofoed, J.;
Nielsen, J.; Reymond, J. L. Bioorg. Med. Chem. Lett. 2003, 13, 2445. (k)
Chan, V.; Kim, J. G.; Jimeno, C.; Carroll, P. J.; Walsh, P. J. Org. Lett.
2004, 6, 2051. (l) Hayashi, Y.; Tsuboi, W.; Shoji, M.; Suzuki, N.
Tetrahedron Lett. 2004, 45, 4353. (m) List, B.; Hoang L.; Martin, H. J.
Proc. Natl. Acad. Sci. U.S.A. 2004, 101, 5839. (n) Northrup, A. B.; Mangion,
I. K.; Hettche F.; MacMillan, D. W. C. Angew. Chem., Int. Ed. 2004, 43,
2152. (o) Tang, Z.; Jiang, F.; Cui, X.; Gong, L. Z.; Mi, A. Q.; Jiang Y. Z.;
Wu, Y. D. Proc. Natl. Acad. Sci. U.S.A. 2004, 101, 5755. (p) Ender, D.;
Grondal, C. Angew. Chem., Int. Ed. 2005, 44, 2. (q) Kazmaier, U. Angew.
Chem., Int. Ed. 2005, 44, 2186. (r) Samanta, S.; Liu, J.-Y.; Dodda, R.;
Zhao. C.-G. Org. Lett. 2005, 7, 5321.
† Anhui Normal University.
‡ Chinese Academy of Sciences.
(1) Palomo, C.; Oiarbide, M.; Garcia, J. M. Chem. Soc. ReV. 2004, 33,
65.
10.1021/ol061418q CCC: $33.50
© 2006 American Chemical Society
Published on Web 09/02/2006

seldom applied in practical synthesis, presumably because
of their narrow substrate scope. To achieve highly catalytic
activity and excellent enantioselectivity of organic reactions
in water, much effort has been devoted to understanding the
nature of the interrupting ionic interactions, hydrogen bonds,
and hydrophobic interactions in aqueous media.7 Very
recently, Takabe8 and Hayashi9 independently reported highly
diastereo- and enantioselective direct aldol reactions in water.
Nonetheless, development of new organocatalysts for the
direct asymmetric aldol reactions in water is still warranted
to achieve high reactivity and high diastereo- and enanti-
oselectivity, as well as catalyst recovery and reuse.
resulting in the corresponding anti aldol products in a nearly
optically pure form.
Prolyl N-sulfonamides (C2) have been used in some
catalytic asymmetric reactions.14 Structurally similar to
proline (C1) and N-(2-pyrrolidinylmethyl)sulfonamides (C3),15
these compounds (C2) are expected to have a broad range
of applications in asymmetric catalysis (Figure 1). We
Dendrimers are well-defined macromolecules with con-
trollable structures, which offer a unique tool for fine-tuning
catalytic activity through their microenviroment. Other
advantages of dendritic catalysts include the combination of
both homogeneous and heterogeneous catalysis10 and pos-
sibile catalyst recovery by using membrane, nanofiltration
techniques11 or selective precipitation.12 Recently, we have
reported the synthesis of some new polyether dendritic chiral
pyrrolidinylmethanol derivatives and their applications in
catalytic asymmetric reactions.13 Herein, we wish to report
that the recyclable chiral amphiphilic dendritic catalysts
derived from prolyl N-sulfonamides catalyze highly diaste-
reo- and enantioselective direct aldol reactions in water,
Figure 1. Structure of proline and its devative organocatalysts.
hypothesized that the prolyl N-sulfonamide compounds (C2)
with polyether dendritic wedges as hydrophobic groups
should assemble with hydrophobic reactants in water and
sequester the transition state from water and, therefore, high
asymmetric induction may be achieved in water.8,9 Thus, we
synthesized a series of chiral dendritic catalysts derived from
prolyl N-sulfonamides and investigated their catalytic activi-
ties in the asymmetric direct aldol reaction in water.
The synthetic procedures for dendritic catalysts 1d-f are
shown in Scheme 1. The reaction of Boc-L-proline with
(3) (a) Organic Synthesis in Water; Grieco, P. A., Ed.; Blackie: London,
1998. (b) Lindstrom, U. M. Chem. ReV. 2002, 102, 2751. (c) Kobayashi,
S.; Manabe, K. Acc. Chem. Res. 2002, 35, 209. (d) Li, C.-J. Chem. ReV.
2005, 105, 3095.
(4) Shibasaki, M.; Matsunaga, S.; Kumagai, N. In Modern Aldol
Reactions; Mahrwald, R., Eds.; Wiley-VCH: Weinheim, 2004; Vol. 2, p
197.
Scheme 1
(5) Dickerson, T. J.; Janda, K. D. J. Am. Chem. Soc. 2002, 124, 3220.
(6) (a) Machajewski, T. D.; Wong, C.-H. Angew. Chem., Int. Ed. 2000,
39, 1352. (b) Wymer, N.; Toone, E. J. Curr. Opin. Chem. Biol. 2000, 4,
110. (c) Zhong, G.; Lerner, R. A.; Barbas, C. F., III. Angew. Chem., Int.
Ed. 1999, 38, 3738.
(7) Sinou, D. AdV. Synth. Catal. 2002, 344, 221.
(8) (a) Mase, N.; Nakai, Y.; Ohara, N.; Yoda, H.; Takabe, K.; Tanaka,
F.; Barbas, C. F. J. Am. Chem. Soc. 2006, 128, 734. (b) Mase, N.; Watanabe
K.; Yoda, H.; Takabe, K.; Tanaka, F.; Barbas, C. F., III. J. Am. Chem. Soc.
2006, 128, 4966.
(9) Hayashi, Y.; Sumiya, T.; Takahashi, J.; Gotoh, H.; Urushima, T.;
Shoji, M. Angew. Chem., Int. Ed. 2006, 45, 958.
(10) For recent reviews on dendritic catalysts, see: (a) Oosterom, G.
E.; Reek, J. N. H.; Kamer, P. C. J.; van Leeuwen, P. W. N. M. Angew.
Chem., Int. Ed. 2001, 40, 1828. (b) Astruc, D.; Chardac, F. Chem. ReV.
2001, 101, 2991. (c) Crooks, R. M.; Zhao, M.; Sun, L.; Chechik, V.; Yueng,
L. K. Acc. Chem. Res. 2001, 34, 181. (d) Twyman, L. J.; King, A. S. H.;
Martin, I. K. Chem. Soc. ReV. 2002, 31, 69. (e) van Heerbeek, R.; Kamer,
P. C. J.; van Leeuwen, P. W. N. M.; Reek, J. N. H. Chem. ReV. 2002, 102,
3717. (f) Fan, Q.-H.; Li, Y.-M.; Chan, A. S. C. Chem. ReV. 2002, 102,
3385. (g) Caminade, A.-M.; Maraval, V.; Laurent, R.; Majoral, J.-P. Curr.
Org. Chem. 2002, 6, 739. (h) Chen, Y.-C.; Wu, T.-F.; Jiang, L.; Deng,
J.-G.; Liu, H.; Zhu, J.; Jiang, Y.-Z. J. Org. Chem. 2005, 70, 1006.
(11) For an excellent review on the nanofiltration technique in dendritic
catalyst recycling, see: Dijkstra, H. P.; van Klink, G. P. M.; van Koten, G.
Acc. Chem. Res. 2002, 35, 798.
(12) For selected reports on dendritic catalyst recycling by precipitation,
see: (a) Reetz, M. T.; Lohmer, G.; Schwickardi, R. Angew. Chem., Int.
Ed. 1997, 36, 1526. (b) Petrucci-Samija, M.; Guillemette, V.; Dasgupta,
M.; Kakkar, A. K. J. Am. Chem. Soc. 1999, 121, 1968. (c) Hu, Q.-S.; Pugh,
V.; Sabat, M.; Pu, L. J. Org. Chem. 1999, 64, 7528. (d) Fan, Q.-H.; Chen,
Y.-M.; Chen, X.-M.; Jiang, D.-Z.; Xi, F.; Chan, A. S. C. Chem. Commun.
2000, 789. (e) Maraval, V.; Caminade, A.-M.; Majoral, J.-P. Organome-
tallics 2000, 19, 4025. (f) Helms, B.; Liang, C. O.; Haeker, C. J.; Fre´chet,
Jean M. J. Macromolecules 2005, 38, 5411.
4-nitrobenzsulfonamide provided 2, which was then reacted
with 3d-f, followed by deprotecting the Boc group to give
(14) (a) Berkessel, A.; Koch, B.; Lex, J. AdV. Synth. Catal. 2004, 346,
1141. (b) Sunde´n, H.; Dahlin, N.; Ibrahen, I.; Adolfsson, H.; Co´rdova, A.
Tetrahedron Lett. 2005, 46, 3385. (c) Bellis, E.; Vasilatou, K.; Kokotos,
G. Synthesis 2005, 14, 2407. (d) Sunde´n, H.; Ibrahen, I.; Eriksson, L.;
Co´rdova, A. Angew. Chem., Int. Ed. 2005, 44, 4877. (e) Cobb, A. J. A.;
Shaw, D. M.; Longbottom, D. A.; Gold, J. B.; Ley, S. V. Org. Biomol.
Chem. 2005, 3, 84.
(15) (a) Wang, W.; Li, H.; Wang, J. Tetrahedron Lett. 2004, 45, 8229,
1369. (b) Wang, W.; Wang, J.; Li, H. Tetrahedron Lett. 2004, 45, 7235.
(c) Wang, W.; Wang, J.; Li H. Tetrahedron Lett. 2004, 45, 7243. (d) Wang,
W.; Wang, J.; Li H. Org. Lett. 2004, 6, 2817. (e) Wang, W.; Wang, J.; Li
H. Angew. Chem., Int. Ed. 2005, 44. (f) Zu, L.; Wang, J.; Li, H.; Wang,
W. Org. Lett. 2006, 8, 3077-3080.
(13) (a) Liu, X.-Y.; Wu, X.-Y.; Chai, Z.; Wu, Y.-Y.; Zhao, G.; Zhu,
S.-Z. J. Org. Chem. 2005, 70, 7432. (b) Wang, G.-Y.; Liu, X.-Y.; Zhao, G.
Synlett 2006, 1150. (c) Liu, X.-Y.; Li, Y.-W.; Wang, G.-Y.; Chai, Z.; Wu,
Y.-Y.; Zhao, G. Tetrahedron: Asymmetry 2006, 17, 750.
4418
Org. Lett., Vol. 8, No. 20, 2006

1d-f in moderate yields. These ligands were purified by
flash column chromatography and characterized by 1H NMR
spectra, MALDI mass spectrometry, and elemental analyses.
All results were in full agreement with the proposed
structures. Catalysts 1a,16 1b,12a,14c-d and 1c were also
synthesized for comparison of their reactivty and efficiency
with 1d-f (see Supporting Information).
Table 2. Results of Reaction of Various Aldehydes with
Cyclohexanone Catalyzed by 1ea
The catalytic activity of 1a-f for the asymmetric direct
aldol reaction was investigated by performing a model
reaction of 4-nitrobenzaldehyde and cyclohexanone. In our
initial experiment, the reaction was performed in water using
a catalytic amount (10 mol %) of prolyl N-sulfonamide, while
other conditions were the same as reported for organocata-
lyzed direct asymmetric aldol reaction.8a,9 The results are
summarized in Table 1.
time yieldb
eed
anti/sync (%)
entry
R
product
(h)
(%)
1
2
3
4
5
6
7
8
4-O2NC6H4-
3-O2NC6H4-
2-O2NC6H4-
4-F3CC6H4-
4-NCC6H4-
4-FC6H4-
6a
6b
6c
6d
6e
6f
6g
6h
6i
6j
6k
6l
6m
6n
6o
6p
6q
6r
24
24
24
24
24
72
72
72
48
48
72
72
72
48
48
72
24
48
99
99
99
95
97
85
87
91
95
94
57
31
36
82
98
94
98
62
>99:1
97:3
98:2
99:1
>99:1
98:2
99:1
98:2
99:1
98:2
94:6
96:4
99:1
93:7
99:1
98:2
87:13
93:7
>99
>99
99
99
98
95
99
99
97
96
95
96
>99
89
>99
81
94
4-ClC6H4-
4-BrC6H4-
2,4-Cl2C6H3-
C6H5-
Table 1. Effect of Catalyst on the Reaction of
4-Nitrobenzaldehyde with Cyclohexanonea
9
10
11
12
13
14
15
16
17
18
4-MeC6H4-
4-MeOC6H4-
4-BnOC6H4-
1-naphthyl-
2-naphthyl-
2-furanyl-
4- pyridinyl-
cyclohexyl-
catalyst
entry catalyst loading (mol %) (h)
time yieldb
eed
(%)
anti/sync (%)
96
1
2
3
4
5
6
7
8
1a
1b
1c
1d
1e
1f
1e
1e
1e
1e
1e
10
10
10
10
10
10
20
5
24
24
24
24
24
24
20
48
48
24
24
58
66
84
92
99
86
99
99
75
99
99
96:4
97:3
94:6
97:3
99:1
99:1
98:2
97:3
96:4
>99:1
97:3
97
97
94
98
99
99
>99
98
98
>99
97
a The reaction was performed with 1e (0.05 mmol), 4 (0.5 mmol), water
(1 mL), and 5a (0.154 mL, 1.5 mmol) at room temperature. b Combined
yields of isolated diastereomers. c Determined by 1H NMR of the crude
product. d Determined by chiral-phase HPLC analysis of the anti product.
(Table 1, entry 5). The third generation catalyst 1f showed
a comparable selectivity, but a drop in reactivity was
observed (Table 1, entry 6). The higher generation catalysts
1d and 1f are sparingly soluble in water; stable emulsions
were formed upon addition of the aldehyde and cyclohex-
anone with vigorous stirring in water.
9
10e
11f
2
10
10
a The reaction was performed with 1 (0.05 mmol), 4a (76 mg, 0.5 mmol),
water (1 mL), and 5a (0.103 mL, 1.0 mmol) at room temperature.
b Combined yields of isolated diastereomers. c Determined by 1H NMR of
the crude product. d Determined by chiral-phase HPLC analysis of the anti
product. e 3 equiv of 5a was used in this reaction. f 5 equiv of 5a was used
in this reaction.
Thus, catalyst 1e was selected for the subsequent studies.
First, the influence of catalyst loading on the reaction was
examined (Table 1, entries 5 and 7-9). It is found that a
higher enantioselectivity was observed by increasing the
catalyst amount to 20 mol %; the reaction was slightly faster,
but the diastereoselectivity dropped slightly (Table 1, entry
7 vs 5). The reaction slowed remarkably and a significant
drop in diastereoselectivity was observed by decreasing the
catalyst loading to 5 mol % and further to 2 mol %.
Examination of the effects of reactants ratio on the reaction
indicated that 3 equiv of donor cyclohexanone to 1 equiv of
acceptor aldehyde gave the best results (Table 1, entry 10).
Thus, the optimum reaction conditions are achieved by
performing the reaction of 3 equiv of cyclohexanone with 1
equiv of aldehyde and 10 mol % catalyst loading in water.
The major product 6a generated from 1e has (2S,1R)8a
absolute stereochemistry. Therefore, the enamine intermedi-
ate catalyzed by 1e favors a re-facial attack on the arylal-
dehyde, which is in accord with that of L-proline-catalyzed
aldol reactions in DMSO.8a,17
It is interesting to find that the aldol reaction proceeds
efficiently in water, and excellent results were obtained with
these catalysts. The anti-aldol products were obtained as the
major product in good to excellent yields (58-99%) with
high diastereoselectivity and enantioselectivity. As expected,
the dendritic catalysts 1d-f bearing more hydrophobic
groups showed much better reactivity and higher selectivity
than catalysts 1a-c with less hydrophobic groups. Notably,
the second generation catalyst 1e provided the best results
in isolated yields, diasteroselectivity and enantioselectivity
(16) (a) Cobb, A. J. A.; Shaw, A. M.; Longbottom, D. A.; Gold, J. B.;
Ley, S. V. Org. Biomol. Chem. 2005, 3, 84. (b) Sunde´n, H.; Ibrahem, I.;
Eriksson, L.; Co´rdova, A. Angew. Chem., Int. Ed. 2005, 44, 4877. (c) Bellis,
E.; Vasilatou, K.; Kokotos, G. Synthesis 2005, 14, 2407. (d) Sunde´n, H.;
Dahlin, N.; Ibrahem, I.; Adolfsson, H.; Co´rdova, A. Tetrahedron Lett. 2005,
46, 3385.
Org. Lett., Vol. 8, No. 20, 2006
4419

To examine the scope of the aldol reactions by using the
dendritic catalyst 1e in water, a series of aldehydes were
evaluated under the optimized reaction conditions, and the
results are summarized in Table 2. In general, regardless of
the electronic nature of the aromatic aldehydes, excellent
diastereoselectivities and enantioselectivities were obtained.
For the electon-deficient aromatic aldehydes (Table 2, entries
1-9 and 17), the reaction proceeded smoothly to afford the
aldol adducts in 24 h. For the neutral and electon-rich
aromatic aldehydes (Table 2, entries 11-13), the reactions
commonly required a longer time (72 h), and lower isolated
yields were obtained for electon-rich ones (Table 2, entries
11-13). It is worthy to note that reaction of the aliphatic
cyclohexanecarboxaldehyde with cyclohexanone also af-
forded the corresponding aldol product with an excellent
diastereoselectivity and enantioselectivity under the same
conditions (Table 2, entry 18). Other ketones were also
evaluated under the same conditions, and the aldol products
were obtained in good yields with high enantioselectivities,
albeit with somewhat decreased diastereoselectivities (Table
3).
Table 4. Recovery of Catalyst 1e in the Aldol Reaction of 4aa
yield of
product
yieldb
(%)
recovered
recovery
solvent
eed catalyst
entry catalyst
anti/sync (%)
(%)
1
2
3
4
5
1e
1e
1e
1e
1e
MeOH
Et2O
EA
92
95
99
<50
99
>99:1
>99:1
>99:1
>99:1
>99:1
>99
>99
>99
>99
>99
98
96
90
>99
94
n-hexane
n-hexane/
EtOAce
n-hexane/
EtOAce
n-hexane/
EtOAce
n-hexane/
EtOAce
n-hexane/
EtOAce
6
7
8
9
1ef
1eg
1eh
1ei
99
97
99
99
99:1
99:1
>99
>99
>99
>99
95
97
94
96
99:1
>99:1
a The reaction was performed with 1e (0.05 mmol), 4a (0.5 mmol), water
(1 mL), and cyclohexanone (0.154 mL, 1.5 mmol) at room temperature.
b Combined yields of isolated diastereomers. c Determined by 1H NMR of
the crude product. d Determined by chiral-phase HPLC analysis of the anti
product. e Ratio of n-hexane and EtOAc is 1:1. f Recovered catalyst was
used (cycle 1). g Recovered catalyst was used (cycle 2). h Recovered catalyst
was used (cycle 3). i Recovered catalyst was used (cycle 4).
Table 3. Reaction of Various Ketones with
4-Nitrobenzaldehyde Catalyzed by 1ea
the best one (entry 5). After the completion of the reaction,
catalyst 1e may be quantitatively recovered by simply adding
1:1 n-hexane/EtOAc to the reaction mixture. Furthermore,
it was found that the recovered catalyst may be reused five
times without loss of reactivity and enantioselectivity (Table
4, entries 5-9).
In conclusion, we have synthesized some chiral dendritic
catalysts derived from prolyl N-sulfonamide. The catalysts
may be used in the asymmetric direct aldol reactions in water,
a safe, economical, and environmentally benign solvent, to
generate the products in good to excellent yields (up to 99%)
with excellent diastereoselectivities (up to >99:1) and
enantioselectivities (up to >99%). Furthermore, these den-
dritic catalysts may be recovered and reused without loss of
reactivity.
time yieldb
eed
entry
R1
R2
product
(h)
(%)
anti/sync (%)
1
2
3e
4e
-(CH2)3-
-(CH2)5-
CH3
6s
6t
6u
6v
18
72
72
72
96
79:21
77:23
98
99
87
89
59f
71f
70f
H
CH3
CH3
87:13
a The reaction was performed with 1e (0.05 mmol), 4a (0.5 mmol), water
(1 mL), and 5 (0.154 mL, 1.5 mmol) at room temperature. b Combined yields
1
of isolated diastereomers. c Determined by H NMR of the crude product.
d Determined by chiral-phase HPLC analysis of the anti product. e 20 equiv
of 5 was used in this reaction. f Aldehyde 4a recovery was 35%, 23%, and
26%.
Acknowledgment. Generous financial support from the
National Natural Science Foundation of China, QT Program,
Shanghai Natural Science Council, the Program for NCET
(NCET-04-0590), and Excellent Young Scholars Foundation
of Anhui province (04046079) is gratefully acknowledged.
One major advantage of dendritic catalysts is that they
may be easily separated from reaction mixtures through
precipitation due to the solubility change in different solvents.
Thus, different solvents were tested (Table 4) to precipitate
the dendritic catalysts in an effort to recover the catalyst,
and we found that a cosolvent of n-hexane/EtOAc (1:1) is
Supporting Information Available: General experimen-
tal methods, analytic data and spectra of the corresponding
compounds. This material is available free of charge via the
Internet at http://pubs.acs.org.
(17) (a) Sakthivel, K.; Notz, W.; Bui, T.; Barbas, C. F., III. J. Am. Chem.
Soc. 2001, 123, 5260. (b) Nakadai, M.; Saito, S.; Yamamoto, H. Tetrahedron
2002, 58, 8167. (c) Mase, N.; Tanaka, F.; Barbas, C. F., III. Angew. Chem.,
Int. Ed. 2004, 43, 2420. (d) Bahmanyar, S.; Houk, K. N.; Martin, H. J.;
List, B. J. Am. Chem. Soc. 2003, 125, 2475.
OL061418Q
4420
Org. Lett., Vol. 8, No. 20, 2006