Development of catalytic asymmetric reactions focussing on fluoroorganic compounds

Abstract

Highly enantioselective catalyses for preparing α,α-difluoro-β-hydroxycarboxylates and secondary α-trifluoromethyl alcohols have been developed. Difluoroketene ethyl trimethylsilyl acetal reacts with aldehydes in the presence of chiral boron complexes to afford the aldol adducts with up to 98% ee. The hydrogenation of 1,1,1-trifiuoroalkan-2-one enol acetates using chiral ruthenium catalysts provides the secondary α-trifluoromethyl alcohols of excellent enantiopurity. The trifluoromethylation of carbonyl compounds with TMSCF3 catalyzed by chiral quaternary ammonium fluorides or triaminosulfonium salts was assessed for synthesizing optically active α-trifluoromethyl alcohols including the tertiary alcohols which, unfortunately, gave moderate enantioselection. Throughout the course of our search for asymmetric catalysts for the trifluoromethylation, two types of Lewis bases, chiral phosphoramides and formamides, have been newly synthesized, and their successful application to the allylation of aldehydes with allylic trichlorosilanes is also described, which provide the corresponding homoallylic alcohols with good-to-excellent enantioselectivity.