Stereoselective Synthesis of 2‑Fluoro-1,3-Diols\nvia Lithium Binaphtholate-Catalyzed Aldol–Tishchenko Reaction

Abstract

Lithium binaphtholate,\nreadily prepared from (<i>R</i>)-3,3′-I₂–BINOL and lithium <i>tert</i>-butoxide, efficaciously\ncatalyzed the enantioselective aldol–Tishchenko tandem reaction\nof α-fluoroketones with aldehydes, achieving the enantioselective\nsynthesis of 2-fluoro-1,3-diols with three contiguous stereogenic\ncenters. Kinetic studies revealed that the aldol reaction and the\nsubsequent hemiacetal formation are in equilibrium under the reaction\nconditions and that the lithium binaphtholate catalyst selectively\npromotes hydride shift of one of the eight stereoisomers to produce\n2-fluoro-1,3-diols containing a tetrasubstituted fluorinated carbon\ncenter.