Enantioselective synthesis of O,O-acetal-fused tetracyclic scaffolds with fluorinated tetrasubstituted centers via fluorine-assisted asymmetric induction

Abstract

Fluorinated molecules hold prominent significance in pharmaceutical chemistry. However, the construction of complex fluorinated compounds bearing multiple chiral centers has long remained a challenge in organic synthesis. Herein, we report an efficient organocatalytic asymmetric strategy for accessing a series of O,O-acetal fused tetracyclic scaffolds featuring fluorinated tetrasubstituted centers, which exhibit excellent diastereoselectivity (>20 : 1 dr) and enantioselectivity (up to 99% ee). The reaction proceeds via an asymmetric multistep cascade sequence, ultimately affording O,O-acetal fused tetracyclic scaffolds bearing both fluorinated tetrasubstituted centers and five consecutive stereocenters. Notably, the hydrogen-bonding interaction of the fluorine atom plays a crucial role in this transformation.