Oxa-Ferrier Rearrangement Reaction Mediated by TEMPO Cation and NaClO2: Application to the Total Synthesis of Passifetilactones B and C

Abstract

The TEMPO⁺ (2,2,6,6-tetramethylpiperidine-N-oxyl cation) is a versatile chemical species commonly known as an oxidizing reagent. Nevertheless, its capability to act as a Lewis acid has been recently revealed. Here, we report a TEMPO⁺-promoted oxa-Ferrier rearrangement of glycals to chiral α,β-unsaturated δ-lactones using sodium chlorite (NaClO₂) as a cheap and environmentally friendly oxidizing reagent. Since the vinylic oxocarbenium intermediate is trapped by chlorite ion to form a carbonyl group, we name this reaction as the “Oxa-Ferrier rearrangement”. Accordingly, this reaction is suitable for various O-acetylated, O-benzoylated, and O-benzylated glycals, providing the corresponding α,β-unsaturated δ-lactones in moderate to good yield. Additionally, the synthetic utility of this methodology was applied to the synthesis and confirmation of the absolute configuration of passifetilactones B and C.