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

Abstract

AbstractThe 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 α‐disubstituted aldehydes followed by a diastereoselective copper‐catalyzed decarboxylative aldol reaction. Reduction of the generated β‐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.