Mechanistic Investigations of Chiral Lithium Binaphtholate Catalysis for Asymmetric Aldol–Tishchenko Reaction of α‑Fluoroarylketones

In
this study, we analyzed the asymmetric aldol-Tishchenko reaction
of α-fluoroarylketones with aldehydes in the presence of chiral
lithium binaphtholate, which was readily prepared from a chiral BINOL
derivative and lithium tert-butoxide. This tandem
reaction afforded enantiomerically enriched 2-fluoro-1,3-diols with
three contiguous stereogenic centers in high yield and with high diastereo-
and enantioselectivities. Moreover, mechanistic investigations of
the lithium binaphtholate-catalyzed enantioselective aldol-Tishchenko
reaction were performed based on the kinetic isotope effect and computational
analyses.