A novel chiral lead(II) catalyst for enantioselective aldol reactions in aqueous media [13]

Full text of DOI:10.1021/ja001234l

J. Am. Chem. Soc. 2000, 122, 11531-11532
11531
cations and have found that rare earths and some other cations
such as Fe2+, Cu2+, Zn2+, Cd2+, Pb2+ are stable and work as Lewis
acid catalysts in water.3g The second issue is the instability of
chiral ligand-coordinated metal complexes in water. Since many
chiral ligand-coordinated metal complexes are decomposed rapidly
in water, we decided to utilize muticoordination system and to
select chiral crown ethers as chiral ligands.
A Novel Chiral Lead(II) Catalyst for Enantioselective
Aldol Reactions in Aqueous Media
Satoshi Nagayama and Shuj Kobayashi*
Graduate School of Pharmaceutical Sciences
The UniVersity of Tokyo, CREST
Japan Science and Technology Corporation (JST)
Hongo, Bunkyo-ku, Tokyo 113-0033 Japan
Chiral crown ethers 1-3 were synthesized according to the
ReceiVed April 10, 2000
Catalytic asymmetric reactions provide one of the most efficient
methods for the preparation of optically active compounds.1 While
several excellent chiral catalysts have been developed recently,
most of them have to be used in strictly anhydrous organic
solvents although organic reactions in aqueous media leading to
benign chemical synthesis are now of great interest.2 This is
probably due to the instability of many catalysts and intermediates
in the presence of even a small amount of water. To address this
issue, we have continued fundamental research on organic
reactions in aqueous media.3 In this paper, we report the design
and synthesis of a novel chiral lead(II) catalyst that can be used
in asymmetric aldol reactions in aqueous media. A general idea
for designing chiral catalysts in aqueous media is also proposed.
Catalytic asymmetric aldol reactions are one of the most
powerful carbon-carbon bond-forming methodologies that afford
synthetically useful chiral â-hydroxy ketones and esters.4 Chiral
Lewis acid-catalyzed reactions of silyl enol ethers with aldehydes
(the Mukaiyama reaction)5 are among the most convenient and
promising, and several successful examples have been reported
since the first chiral tin(II)-catalyzed reactions appeared in 1990.6
However, the use of aprotic anhydrous solvents as well as low
reaction temperatures (-78 °C) has been needed in almost all
successful cases.7 To perform catalytic asymmetric aldol reactions
successfully in aqueous media,8 two problems to be addressed
were assumed. First, many cations (Lewis acids) hydrolyze very
easily in water. To overcome this problem, we screened various
literature methods,9 and combination with metals was examined
on the basis of ionic diameters of cations10 and the hole size of
the crown ethers.9,11 Chiral catalysts were prepared by mixing
metal compounds and the crown ethers and were tested in a model
aldol reaction of the (Z)-silyl enol ether of propiophenone (4)
with benzaldehyde in water-ethanol (1:9) at 0 °C. The results
are summarized in Table 1. When Cu(OTf)2 or Zn(OTf)2 was
combined with 1,12 the aldol reaction proceeded smoothly to afford
the corresponding adduct in high yield albeit no chiral induction
was observed. According to the diameters and the hole size, we
next examined the combination of Sc(OTf)3 or Yb(OTf)3 and 2.13
Although these rare earth metal triflates are known to be excellent
Lewis acid catalysts in aqueous media,14 no chiral induction was
detected in the model aldol reaction. We then studied the use of
AgOTf or Pb(OTf)2 and 3.15 While no chiral induction was
observed using AgOTf-3, it was exciting to find that the aldol
reaction proceeded smoothly using Pb(OTf)2-3 to afford the
corresponding adduct in 62% yield with high syn-selectivity (syn/
anti ) 90/10) and that the enantiomeric excess of the syn-adduct
was 55%. It should be noted that the hole size of the crown ether
is essential because no chiral induction was observed in the same
model aldol reaction using the combination of Pb(OTf)2 and 1 or
2. It was also found that the counteranions of lead (II) strongly
influenced the selectivity. While the same level of enantioselec-
tivity was obtained by using Pb(ClO4)2 and 3, lower enantiomeric
excesses (ee’s) were observed when Pb(NO3)2 or Pb(SbF6)2 and
3 were used. When Pb(BF4)2, Pb(PF6)2, or PbF2 was employed,
the model aldol reactions proceeded sluggishly.
(1) Jacobsen, E. N., Pfaltz, A., Yamamoto, H., Eds. ComprehensiVe
Asymmetric Catalysis; Springer: Heidelberg, 1999.
(2) (a) Grieco, P., Ed. Organic Reactions in Water; Chapman & Hall, 1998.
(b) Li, C.-J.; Chan, T.-H. Organic Reactions in Aqueous Media; Wiley: New
York, 1997. (c) Lubineau, A.; Auge´, J.; Queneau, Y. Synthesis 1994, 741. (d)
Li, C.-J. Chem. ReV. 1993, 93, 2023. (e) Reissig, H.-U. In Organic Synthesis
Highlights; Waldmann, H., Ed. VCH: Weinheim, 1991; p 71. (f) Einhorn,
C.; Einhorn, J.; Luche, J. Synthesis 1989, 787.
The effect of solvents was then examined.16 The aldol reaction
proceeded most efficiently in a water-alcohol solution. 2-Pro-
panol was the best alcohol, and much lower yield and selectivities
were obtained when the reaction was carried out in dichlo-
romethane. In pure water (without alcohols), lower yield and
selectivities were also observed, while the diastereo- and enan-
tioselectivities were improved in the presence of a surfactant.17
Other substrates were also successfully used in this system (Pb-
(3) (a) Kobayashi, S. Chem. Lett. 1991, 2187. (b) Hachiya, I.; Kobayashi,
S. J. Org. Chem. 1993, 58, 6958. (c) Kobayashi, S.; Hachiya, I. J. Org. Chem.
1994, 59, 3590. (d) Kobayashi, S.; Ishitani, H. J. Chem. Soc., Chem. Commun.
1995, 1379. (e) Kobayashi, S.; Wakabayashi, T.; Nagayama, S.; Oyamada,
H. Tetrahedron Lett. 1997, 38, 4559. (f) Kobayashi, S. In Organic Reactions
in Water; Grieco, P., Ed.; Chapman & Hall: London, 1998; pp 262-305. (g)
Kobayashi, S.; Nagayama, S.; Busujima, T. J. Am. Chem. Soc. 1998, 120,
8287. (h) Manabe, K.; Mori, Y.; Kobayashi, S. Synlett 1999, 1401. (i)
Nagayama, S.; Kobayashi, S. Angew. Chem., Int. Ed. 2000, 39, 567. See also
ref 8.
(4) (a) Carreira, E. M. In ComprehensiVe Asymmetric Catalysis; Jacobsen,
E. N., Pfaltz, A., Yamamoto, H., Eds.; Springer: Heidelberg, 1999; Vol. 3, p
998. (b) Mahrwald, R. Chem. ReV. 1999, 99, 1095. (c) Gro¨ger, H.; Vogl, E.
M.; Shibasaki, M. Chem. Eur. J. 1998, 4, 1137. (d) Nelson, S. G.
Tetrahedron: Asym. 1998, 9, 357. (e) Bach, T. Angew. Chem., Int. Ed. Engl.
1994, 33, 417.
(5) Mukaiyama, T.; Narasaka, K.; Banno, K. Chem. Lett. 1973, 1012.
(6) (a) Kobayashi, S.; Fujishita, Y.; Mukaiyama, T. Chem. Lett. 1990, 1455.
(b) Mukaiyama, T.; Kobayashi, S.; Uchiro, H.; Shiina, I. Chem. Lett. 1990,
129.
(9) Kyba, E. P.; Helheson, R. C.; Madan, K.; Gokel, G. W.; Tarnowski, T.
L.; Moore, S. S.; Cram, D. J. J. Am. Chem. Soc. 1977, 99, 2564.
(10) (a) Shannon, R. D.; Prewitt, C. T. Acta Crystallogr. 1969, B25, 925.
(b) Shannon, R. D. Acta Crystallogr. 1976, A32, 751.
(11) Kyba, E. P.; Gokel, G. W.; de Jong, F.; Koga, K.; Sousa, L. R.; Siegel,
M. G.; Kaplan, L.; Sogah, G. D. Y.; Cram, D. J. J. Org. Chem. 1977, 42,
4173.
(12) Ionic diameters of Cu2+ and Zn2+ are 144 pm and 148 pm,
respectively.10 The hole size of 12-crown-4 was reported to be 120-150 pm.
Vo¨gtle, F. Supramolecular Chemistry: An Introduction; John Wiley & Sons:
Chichester, 1989.
(7) Some catalytic asymmetric aldol reactions were performed at higher
temperatures (-20-23 °C). (a) Mikami, K.; Matsukawa, S. J. Am. Chem.
Soc. 1993, 115, 7039. (b) Carreira, E. M.; Singer, R. A.; Lee, W. J. Am.
Chem. Soc. 1994, 116, 8837. (c) Keck, G. E.; Krishnamurthy, D. J. Am. Chem.
Soc. 1995, 117, 2363. Catalytic asymmetric aldol reactions in wet dimethyl-
formamide were reported. (d) Sodeoka, M.; Ohrai, K.; Shibasaki, M. J. Org.
Chem. 1995, 60, 2648.
(13) Ionic diameters of Sc3+ and Yb3+ are 162 pm and 172 pm,
respectively.10 The hole size of 15-crown-5 was reported to be 170-220 pm.
(14) (a) Kobayashi, S. Synlett 1994, 689. (b) Kobayashi, S. Eur. J. Org.
Chem. 1950, 15, 5.
(15) Ionic diameters of Ag+ and Pb2+ are 252 pm and 240 pm, respec-
tively.10 The hole size of 18-crown-6 was reported to be 260-320 pm.
(16) Details are shown in Supporting Information.
(8) (a) Kobayashi, S.; Nagayama, S.; Busujima, T. Chem. Lett. 1999, 71.
(b) Kobayashi, S.; Nagayama, S.; Busujima, T. Tetrahedron 1999, 55, 8739.
10.1021/ja001234l CCC: $19.00 © 2000 American Chemical Society
Published on Web 11/04/2000

11532 J. Am. Chem. Soc., Vol. 122, No. 46, 2000
Table 1. Effect of Metal-Ligand Combinationsa
Communications to the Editor
MXn
ligand
yield (%)
syn/anti
ee (%)a
Zn(OTf)2
Cu(OTf)2
Sc(OTf)3
Yb(OTf)3
AgOTf
Pb(OTf)2
Pb(OTf)2
Pb(OTf)2
1
1
2
2
3
3
1
2
88
86
75
74
61
62
78
92
69/31
87/13
52/48
63/37
75/25
90/10
89/11
89/11
2
0
1
1
5
55
0
0
a ee of syn-adduct.
(OTf)2-3, 20 mol %; water-2-propanol (1:4.5), 0 °C).18 In the
reactions with 4, the results are as follows: p-chlorobenzaldehyde
(74% yield, syn/anti ) 82:18, 62% ee (syn)); hexanal (82% yield,
syn/anti ) 92:8, 80% ee (syn)); 1-nonanal (79% yield, syn/anti
) 90:10, 82% ee (syn)); isovaleraldehyde (99% yield, syn/anti
) 94:6, 87% ee (syn)); 2-methylpropionaldehyde (65% yield, syn/
anti ) 90:10, 78% ee (syn)); 2-thiophenecarboxaldehyde (67%
yield, syn/anti ) 90:10, 75% ee (syn)). The reaction also
proceeded smoothly using 10 mol % of Pb(OTf)2-3 (88% yield,
syn/anti ) 93/7, 85% ee (syn) in the reaction of isovaleraldehyde
with 4). It should be noted that good to high yields and high
levels of diastereo- and enantioselectivities were obtained at 0
°C in aqueous media and that even aliphatic aldehydes worked
well under these reaction conditions. In the reaction of benzal-
dehyde with the silyl enolate derived from (S)-ethyl propaneth-
ioate, 51% yield was obtained with syn/anti ) 93/7 (47% ee
(syn)).19
The key to this catalytic asymmetric aldol reaction is a novel
chiral lead(II) catalyst. The solid-state structure of Pb(OTf)2-3
was determined by single-crystal X-ray diffraction (Figure 1).16,20
The lead atom is coordinated by the six oxygens of the crown
ether, two triflates, and one water. A characteristic point is that
one Pb-O bond (310.9 pm) is much longer than others.21 The
oxygen atom is directly connected to the binaphthyl ring of 3,
and the long length is ascribed to the dihedral angle between the
two naphthalene rings of 3, which create an excellent asymmetric
environment in the lead(II) catalyst. The high selectivities obtained
would be explained by assuming that the water coordinating to
lead(II) is replaced by aldehydes under the reaction conditions3g
and that silyl enolates attack the aldehydes to afford the (2S,3S)-
adduct.22
Figure 1. Pb(OTf)2-crown ether 3 (X-ray).
water-ethanol (1:4.5) and Pb(OTf)2-catalyzed achiral reaction in
the same solvent system.16 It was very interesting to find that
almost comparable reaction rates between the above two systems
were observed. In addition, the same levels of diastereo- and
enantioselectivities were obtained during the reaction course in
the Pb(OTf)2-3-catalyzed reactions. These results indicate that
suitable combinations of metal-chiral crown ether complexes
provide promising chiral catalysts in aqueous media.
In summary, we have developed Pb(OTf)2-crown ether 3 as
an efficient chiral catalyst for asymmetric aldol reactions in
aqueous media. To the best of our knowledge, this is the first
example of a chiral crown-based Lewis acid23 that can be
successfully used in catalytic asymmetric reactions. It should be
noted that the novel chiral catalyst was successfully used in
aqueous media. The catalyst has been characterized by X-ray
diffraction, and its unique structure as a chiral catalyst has been
revealed. A kinetic study has shown potential utility of these types
of chiral catalysts which can be employed in aqueous media.
Investigations along this line are now in progress in our laboratory.
Acknowledgment. This work was partially supported by a Grant-
in-Aid for Scientific Research from the Ministry of Education, Science,
Sports, and Culture, Japan. S.N. thanks the JSPS fellowship for Japanese
Junior Scientists.
Supporting Information Available: Experimental details (PDF). This
material is available free of charge via the Internet at http://pubs.acs.org.
JA001234L
Finally, a preliminary kinetic study was performed in the
following two systems: Pb(OTf)2-3-catalyzed aldol reaction in
(20) (a) Drew, M. G. B.; Nicholson, D. G.; Sylte, I.; Vasudevan, A. K.
Acta Chem. Scand. 1992, 46, 396. (b) von Arnim, H.; Dehnicke, K.; Maczek,
K.; Fenske, D. Z. Anorg. Allg. Chem. 1993, 619, 1704. (c) Simonov, Y. A.;
Kravtsov, V. K.; Fonar’, M. S.; Nazarenko, A. Y. Russ. J. Inorg. Chem. 1996,
41, 371.
(17) Kobayashi, S.; Wakabayashi, T.; Nagayama, S.; Oyamada, H.
Tetrahedron Lett. 1997, 38, 4559.
(18) Experimental procedures are described in Supporting Information. Pb-
(OTf)2 was recovered quantitatively by simple extraction, and chiral crown
ether 3 was also recoverable. The authors are grateful to Mr. Tomoaki Hamada
(The University of Tokyo) for his technical support.
(19) Although the reaction conditions have not been optimized, this is the
first example of the catalytic asymmetric aldol reaction of a silyl enolate
derived from a thioester (water-sensitive enolate). For other substrates, higher
yields and selectivities were obtained in most cases compared to those in the
previous report.8
(21) One of two bonds between Pb and the oxygens connected to the
naphthalene rings is longer. Details are shown in Supporting Information.
(22) The absolute configulation was determined by comparison with the
authentic sample. Denmark, S. E.; Wong, K.-T.; Stavenger, R. A. J. Am. Chem.
Soc. 1997, 119, 2333.
(23) Recently, complexes of lanthanide triflates with achiral polyethers were
prepared and used in allylation and Diels-Alder reactions in dry dichlo-
romethane. Aspinall, H. C.; Dwyer, J. L. M.; Greeves, N.; McIver, E. G.;
Woolley, J. C. Organometallics 1998, 17, 1884.