Multi-catalytic Enantioselective Synthesis of 1,3-Diols Containing a Tetrasubstituted Fluorinated Stereocenter

The enantioselective construction of fluorohydrins featuring a tetrasubstituted stereocenter embedded in complex frameworks represents an important challenge. Herein, we report a multicatalytic strategy enabling the stereoselective preparation of a new type of scaffold containing such a challenging fluorohydrin motif. The sequence is based on an organocatalyzed fluorination of alpha-disubstituted aldehydes followed by a diastereoselective copper-catalyzed decarboxylative aldol reaction. Reduction of the generated beta-hydroxy ketone followed by a Lewis base-catalyzed kinetic resolution enables the isolation of original fluorinated 1,3-diols with perfect diastereo- and enantio-control.