Detrifluoroacetylative cascade reactions of bicyclic fluoro-enolates with ortho-phthalaldehyde: Aspects of reactivity, diastereo- and enantioselectivity

Abstract The development of new asymmetric methods for preparation of chiral fluorine-containing compounds is in extremely high demand in many areas of chemical research and industry. Herein, we describe a new cascade reaction approach, exemplified by the reactions of, in situ generated fluoro-enolates, with ortho -phthalaldehyde. The reactions proceed through the sequence of detrifluoroacetylation, aldol addition, intramolecular cyclization and oxidation, under convenient conditions with synthetically attractive stereochemical outcome and good structural generality. We demonstrate that these cascade reactions can be performed in catalytic asymmetric mode affording diastereomerically pure products with up to 86% ee.