Asymmetric catalysis in aqueous media: Use of metal-chiral crown ethers asefficient chiral Lewis acid catalysts in asymmetric aldol reactions

Metal-chiral crown ether complexes have been developed as efficient chiral Lewis acid catalysts for asymmetric aldol reactions of silyl enol ethers wi th aldehydes in aqueous media. While many excellent catalytic asymmetric re actions have been developed recently, most of them have to be carried out u nder strictly anhydrous conditions in organic solvents. This is probably du e to the instability of many catalysts and/or intermediates in the presence of even a small amount of water. To address this issue, we searched for me tal-crown ether complexes on the basis of our "multi-coordination" hypothes is, and found that lead(II) and lanthanide(III) catalysts worked well as ch iral Lewis acids in aqueous media. To the best of our knowledge, these are the first examples of chiral crown-based Lewis acids that can be successful ly used in catalytic asymmetric reactions. The catalysts have been characte rized by X-ray diffraction, and their unique structures as chiral catalysts have been revealed. Use of water as a solvent is essential in these asymme tric catalysis, and the role of water on these reactions to explain the hig h reactivity and selectivity has been suggested. Another important point is that kinetic studies have shown the possibility that these types of crown ether complexes would be suitable as chiral catalysts employed in aqueous m edia. In addition, although the catalytic asymmetric aldol reactions are on e of the most powerful carbon-carbon bond-forming methodologies and several successful examples have been reported, the use of aprotic anhydrous solve nts and low reaction temperatures (-78 degreesC) has been needed in almost all successful cases. On the other hand, the present reactions proceeded sm oothly at -10-0 degreesC in water-alcohol solutions while retaining high le vels of diastereo- and enantioselectivities.