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

Abstract

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.

Synthesis of Substituted Indolizidines and Quinolizidines by Regioselective Intramolecular Modified Julia Olefination of Imides

“…In this particular case, we showed that in standard conditions the enamide was formed as a single regioisomer but that the nitrophenyl group migrates on the α-position of the carbonyl group during the DBU treatment. This type of reactivity of the nosylamide group has already been reported . We then tried the conditions to form the vinyl sulfone.…”