Development of the titanium-TADDOLate-catalyzed asymmetric fluorination of β-ketoesters.

Titanium-based Lewis acids catalyze the α-fluorination of β-ketoesters by electrophilic N-F-fluorinating reagents. Asymmetric catalysis with TADDOLato-titanium(IV) dichloride (TADDOL = α,α,α',α'-tetraaryl-(1,3-dioxolane-4,5-diyl)-dimethanol) Lewis acids produces enantiomerically enriched α-fluorinated β-ketoesters in up to 91% enantiomeric excess, with either F-TEDA (1-chloromethyl-4-fluoro-1,4-diazoniabicyclo[2.2.

Titanium-catalyzed stereoselective geminal heterodihalogenation of beta-ketoesters.

[reaction: see text] beta-Ketoesters can be effectively monofluorinated with F-TEDA using CpTiCl(3) as a catalyst. With the use of this catalyst, the extent of the competing difluorination does not reach 10%. [TiCl(2)(TADDOLato)] complexes catalyze the one-pot enantioselective heterodihalogenation of beta-ketoesters with F-TEDA and NCS to afford alpha-chloro-alpha-fluoro-beta-ketoesters in moderate to good yields.