Calix[6]arene derivatives bearing sulfonate and alkyl groups as surfactants in Sc(OTf)3-catalyzed Mukaiyama aldol reactions in water

Article abstract of DOI:10.1016/S0040-4039(00)00257-4

Amphiphilic calix[6]arene derivatives 1a-b were found to be efficient surfactants for Sc(OTf)₃-catalyzed Mukaiyama aldol reaction of silyl enol ethers with aldehydes in water. The results indicated that a hydrophobic microenvironment was formed

Full text of DOI:10.1016/S0040-4039(00)00257-4

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 41 (2000) 2529–2532
Calix[6]arene derivatives bearing sulfonate and alkyl groups
as surfactants in Sc(OTf)3-catalyzed Mukaiyama aldol
reactions in water
Hong-Yu Tian,a Yong-Jun Chen,a Dong Wang,a,∗ Cheng-Chu Zeng a and Chao-Jun Li b,∗
aCenter of Molecular Science, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100080, China
bDepartment of Chemistry, Tulane University, New Orleans, LA 70118, USA
Received 19 January 2000; revised 9 February 2000; accepted 10 February 2000
Abstract
Amphiphilic calix[6]arene derivatives 1a–b were found to be efficient surfactants for Sc(OTf)3-catalyzed
Mukaiyama aldol reaction of silyl enol ethers with aldehydes in water. The results indicated that a hydrophobic
microenvironment was formed in the reaction system, which is favorable to stabilize some labile silyl enol ethers
and thus promotes the reactions. © 2000 Elsevier Science Ltd. All rights reserved.
The development of carbon–carbon bond-forming reactions in aqueous media is a challenging topic in
organic synthesis.1 The aldol-type reaction of silyl enol ethers with carbonyl compounds (the Mukaiyama
reaction)2 has been recognized as one of the most important carbon–carbon bond-forming reactions.
Recently, great progress has been made on aqueous Mukaiyama aldol reactions by using a series of water-
tolerant Lewis acids, such as lanthanide triflates, and metal salts.3 As Kobayashi4 reported, in order to
promote the reactions in water alone, certain surfactants must be added to the lanthanide triflate catalyzed-
reaction medium, such that a micellar system is formed. These surfactants can be anionic, such as sodium
dodecyl sulfate (SDS), or nonionic. However, although some very labile silyl enol ethers could react
smoothly with aldehydes in water in the presence of a surfactant Lewis acid, scandium trisdodecylsulfate
(STDS),5 they decompose rapidly in the Sc(OTf)3–SDS–H2O system. For improving the reaction yield,
it is necessary to use a large excess of the very labile silyl enol ethers in the Sc(OTf)3–SDS–H2O system.4
Previously, Shinkai and co-workers6 reported the synthesis and inclusion properties of some water-
soluble calixarene derivatives with surfactant activity. It was found that the water-soluble p-sulfonated
calixarenes could form host–guest type complexes with various organic guest molecules in water with the
aid of hydrophobic interactions. We envisioned that the use of these calixarene derivatives as surfactants
in the aqueous Mukaiyama aldol reaction would provide a hydrophobic cavity, which would be favorable
to stabilize the labile silyl enol ethers and prevent them from being hydrolyzed in water. Herein, we
wish to report that the calix[6]arenes 1a and 1b (bearing both sulfonates and alkyl groups) are efficient
∗
Corresponding authors. E-mail: g210@mimi.cnc.ac.cn
0040-4039/00/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)00257-4
tetl 16537

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surfactants in Sc(OTf)3-catalyzed Mukaiyama reactions in water (Eq. (1)). The use of these surfactants
can inhibit the hydrolysis of silyl enol ethers as well as promote the carbon–carbon bond formation
reaction.
Calix[6]arene derivatives 1a–b, bearing sulfonate groups on the upper rim and the hydrophobic alkyl
groups on the lower rim, were synthesized based upon the protocol by Shinkai.6 At the beginning of the
investigation the aldol reactions of silyl enol ethers, 1-trimethylsiloxy-cyclohex-1-ene (3a) and 1-phenyl-
1-trimethylsiloxyethylene (3b), with aldehydes 2a–d were carried out in water at room temperature in
the presence of the surfactants 1a–b (20 mol%) and the catalyst Sc(OTf)3 (10 mol%) to afford the aldol
adducts 4a–f (Eq. (1)).7 For comparison, the Sc(OTf)3-catalyzed reactions in water were also examined
with 20 mol% of the surfactant SDS instead of 1a–b. The experimental results are summarized in Table
1. In the case of SDS, the silyl enol ethers 3a–b in the reaction mixture disappeared (as shown by TLC)
after 1 h of the reaction; however, a large amount of the aldehyde remained, leading to lower yields of the
aldol products. In contrast, when surfactants 1a and 1b were used, the silyl enol ethers 3a and 3b were
still present after a longer reaction time in aqueous solution. Presumably, such an increased stability of
the silyl enol ethers toward water in the presence of 1a and 1b resulted in higher yields of the aldol
products. The calix[6]arene derivative 1b, having a hexyl group exhibited an advantage over 1a which
bears a shorter chain (butyl group) in both reaction rates and yields (a shorter reaction time and a higher
yield). This difference can be explained by the fact that the calix[6]arenes bearing alkyl groups on the
lower rim could form a hydrophobic cavity, which associates with the molecule of the silyl enol ether
in water. This complex effectively shields the labile silyl enol ethers from hydrolysis and increases the
concentration of silyl enol ethers in the hydrophobic reaction field. The size of the cavity formed by 1b
with a longer chain is larger and better accommodates the molecule of silyl enol ethers.
(1)
Then, surfactants 1a–b were examined for the aldol reactions of 1-phenyl-1-trimethylsiloxypropene
(3c) (R2=Ph, R3=CH3) with aldehydes in water by the same experimental procedure. The results are
summarized in Table 2. Since 3c is relatively stable to water, both the calix[6]arene surfactants 1a–b and
SDS gave high yields of the aldol adducts 4g–k. However, if a sulfonated calix[6]arene without alkyl
groups on the lower rim (1c, R=H) was used instead of 1a–b, the aldol reactions of 3c with aldehydes
did not proceed at all and 3c was still present in the 1c–Sc(OTf)3–H2O system even after 10 h of stirring.
These results indicate that the alkyl group on the lower rim does not only play a role in stabilizing the silyl
enol ethers, but also promotes the aldol reaction in water. Comparing 1a with 1b, 1a is less effective in
promoting the aldol reaction of 3c (a longer reaction time) but gave a slightly higher diastereoselectivity
(syn/anti) of the aldol products. It can be assumed that 1a, having a shorter alkyl chain, results in a

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Table 1
Aldol reactions of 3a–b with aldehydes in water using 1a–b and SDS as surfactants
Table 2
Aldol reaction of 3c with aldehydes in water using 1a–b and SDS as surfactants

2532
hydrophobic cavity which is too small to accommodate both substrates properly but is favorable for
selectively hosting a substrate molecule.
In conclusion, the calix[6]arene derivatives 1a–b were found to be effective surfactants for the aqueous
Mukaiyama aldol reactions of silyl enol ethers with aldehydes catalyzed by Sc(OTf)3 to afford the aldol
products in high yields. Both 1a and 1b can provide a proper size of hydrophobic cavity to host and
stabilize some labile silyl enol ethers in water, and to promote the aqueous aldol reactions.
Acknowledgements
We thank the National Natural Science Foundation of China and the National Laboratory of Elemento-
Organic Chemistry in Nankai University of China for financial support.
References
1. Li, C. J.; Chan, T. H. Organic Reactions in Aqueous Media, Wiley: New York, 1997; Li, C. J. Chem Rev. 1993, 93, 2023; Li,
C. J.; Chan, T. H. Tetrahedron 1999, 55, 11149.
2. Mukaiyama, T.; Narasaka, K.; Banno, T. Chem. Lett. 1973, 1011; Mukaiyama, T.; Banno, K.; Narasaka, K. J. Am. Chem.
Soc. 1974, 96, 7503; Mukaiyama, T. Org. React. 1982, 28, 203.
3. Kobayashi, S. In Lanthanides: Chemistry and Use in Organic Synthesis; Kobayashi, S., Ed. Lanthanide triflate-catalyzed
carbon–carbon bond-forming reactions in organic synthesis. Springer: Berlin, 1999, and references cited therein; Kobayashi,
S.; Nagayama, S.; Busujima, T. J. Am. Chem. Soc. 1998, 120, 8287; Kobayashi, S.; Nagayama, S.; Busujima,T. Tetrahedron
1999, 55, 8739; Loh, P.; Li, X.-R. Tetrahedron 1999, 55, 10789; Lubineau, A.; Auge, J.; Queneau, Y. Synthesis 1994, 741.
4. Kobayashi, S.; Wakabayashi, T.; Nagayama, S.; Oyamada, H. Tetrahedron Lett. 1997, 38, 4559.
5. Kobayashi, S.; Wakabayashi, T. Tetrahedron Lett. 1998, 39, 5389; Manabe, K.; Mori, Y.; Kobayashi, S. Tetrahedron 1999,
55, 11203.
6. Shinkai, S.; Mori, S.; Koreishi, H.; Mannabe, O. J. Am. Chem. Soc. 1986, 108, 2409; Shinkai, S.; Araki, K.; Manabe, O. J.
Chem. Soc., Chem. Commun. 1988, 187; Shinkai, S.; Kawabata, H.; Arimura, T.; Matsuda, T. J. Chem. Soc., Perkin Trans. 1
1989, 1073; Shinkai, S., Arimura, T.; Araki, K.; Kawabata, H. J. Chem. Soc., Perkin Trans. 1 1989, 2039.
7. A typical experimental procedure: To a mixture of the surfactant (0.04 mmol) in water (1 mL) was added Sc(OTf)3 (0.02
mmol), aldehyde (0.2 mmol), and the silyl enol ether (0.3 mmol). The mixture was stirred at room temperature until the silyl
enol ether disappeared on TLC. Then the mixture was passed through a short silica gel pad and extracted with ethyl ether.
The combined organic layer was dried over MgSO4 and concentrated under reduced pressure. The residue was purified by
flash chromatography on silica gel to afford the desired aldol adduct.