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

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(NO3)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 α,β-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.