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

J Org Chem. 2024 Dec 6;89(23):17101-17114. doi: 10.1021/acs.joc.4c01404. Epub 2024 Nov 8.

Abstract

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.