Fluoride-Mediated Desulfonylative Intramolecular Cyclization to Fused and Bridged Bicyclic Compounds: A Complex Mechanism

We previously reported the synthesis of polysubstituted chiral oxazepanes in three steps from commercially available starting materials. The unexpected reaction of one of these 1,4-oxazepanes in the presence of TBAF provided a 4-oxa-1-azabicyclo[4.1.0]­heptane core. This unusual process significantly increased the complexity of the molecular scaffold by introducing a bicyclic core. Surprisingly, the generated bicyclic structure featuring three stereocenters was a mixture of enantiomers with no other diastereomers observed. These striking experimental observations deserved further investigations. A combination of experimental and computational investigations unveiled a complex diastereoselective mechanism. Mechanistic rationale is presented for this observed rearrangement.