Development of the titanium-TADDOLate-catalyzed asymmetric fluorination of beta-ketoesters

作者：Hintermann Lukas; Perseghini Mauro; Togni Antonio^*

来源：Beilstein Journal of Organic Chemistry, 2011, 7: 1421-1435.

DOI：10.3762/bjoc.7.166

• Asymmetric catalysis
• fluorination
• fluoroorganic compounds
• TADDOL
• titanium

Titanium-based Lewis acids catalyze the alpha-fluorination of beta-ketoesters by electrophilic N-F-fluorinating reagents. Asymmetric catalysis with TADDOLato-titanium(IV) dichloride (TADDOL = alpha,alpha,alpha',alpha'-tetraaryl-(1,3-dioxolane-4,5-diyl)-dimethanol) Lewis acids produces enantiomerically enriched alpha-fluorinated beta-ketoesters in up to 91% enantiomeric excess, with either F-TEDA (1-chloromethyl-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate)) in acetonitrile solution or NFSI (N-fluorobenzenesulfonimide) in dichloromethane solution as fluorinating reagents. The effects of various reaction parameters and of the TADDOL ligand structure on the catalytic activity and enantioselectivity were investigated. The absolute configuration of several fluorination products was assigned through correlation. Evidence for ionization of the catalyst complex by chloride dissociation, followed by generation of titanium beta-ketoenolates as key reaction intermediates, was obtained. Based on the experimental findings, a general mechanistic sketch and a steric model of induction are proposed.

• 出版日期2011-10-17