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.