Catalytic Asymmetric Aldol Reactions in Aqueous Media Using Chiral Bis-pyridino-18-crown-6−Rare Earth Metal Triflate Complexes

Abstract

Catalytic asymmetric aldol reactions in aqueous media have been developed using Pr(OTf)(3) and chiral bis-pyridino-18-crown-6 1. In the asymmetric aldol reaction using rare earth metal triflates (RE(OTf)(3)) and 1, slight changes in the ionic diameters of the metal cations greatly affected the diastereo- and enantioselectivities of the products. The substituents (MeO, Br) at the 4-position of the pyridine rings of the crown ether did not significantly affect the selectivities in the asymmetric aldol reaction, although they affected the binding ability of the crown ether with RE cations and the catalytic activity of Pr(OTf)(3)-crown ether complexes. From X-ray structures of RE(NO(3))(3)-crown ether complexes, it was found that they had similar structures regardless of the RE cations and the crown ethers used. Accordingly, the binding ability of the crown ether with the RE cation and the catalytic activity of the complex are important for attaining high selectivity in the asymmetric aldol reaction. Various aromatic and alpha,beta-unsaturated aldehydes and silyl enol ethers derived from ketones and a thioester can be employed in the catalytic asymmetric aldol reactions using Pr(OTf)(3) and 1, to provide the aldol adducts in good to high yields and stereoselectivities. In the case using the silyl enol ether derived from the thioester, 2,6-di-tert-butylpyridine significantly improved the yields of the aldol adducts.

Aqueous Asymmetric Mukaiyama Aldol Reaction Catalyzed by Chiral Gallium Lewis Acid with Trost‐Type Semi‐Crown Ligands

“…Aldol products, 4a, [3] 4b, [8] 4c, [5] 4d, [4] 4e, [3] 4f, [5] 4g, [8] 4h, [4] 7a, [7] 7b, [9] 7c, [10] 7d, [11] 7e, [12] 10a, [6] 10b, [5] 13a, [4] 13c, [5] 13e [5] are known compounds.…”

Efficient Heterogeneous Asymmetric Catalysis of the Mukaiyama Aldol Reaction by Silica‐ and Ionic Liquid‐Supported Lewis Acid Copper(II) Complexes of Bis(oxazolines)

“…In molecular solvents the yield of aldol product formed is shown to be dependent on catalyst concentration, [29] silyl ether geometry [30] and concentration of water. [31] However, in these cases, even though the product yields were diminished there was no report of the formation of the self-condensation product that was obtained in ionic liquid, as described above.…”

Asymmetric Mukaiyama-Aldol Reaction in Aqueous Media Promoted by Zinc-Based Chiral Lewis Acids

“…Recently, Kobayashi and co-workers developed the combination of RE(OTf) 3 and chiral bis-pyridino-18-crown-6 for the asymmetric Mukaiyama-aldol reaction in aqueous ethanol [ee up to 85% for aromatic enol ether when Pr(OTf) 3 was used as Lewis acid]. [7] In general, the state-of-the-art in this area provides aldol products in good ees (70 -80%). The scope and limitation of this reaction is still not well recognized, and for ee exceeding 80% special ligands have to be chosen.…”

“…The scope and limitation of this reaction is still not well recognized, and for ee exceeding 80% special ligands have to be chosen. [6,7] In general, the elaborated methods fail when aliphatic aldehydes are substrates, although Kobayashi recently presented an excellent example of hydroxymethylation of silicon enolates using an aqueous solution of formaldehyde. [8] In this paper we demonstrate the utility of a zincbased chiral Lewis acid for the enantioselective Mukaiyama-aldol reaction in aqueous media.…”