Strategies for Enantioselective, Cascade, Valorizing, and Expanded Heterocyclic Piancatelli Rearrangements

Abstract

The Piancatelli rearrangement of 2-furylcarbinols has become a versatile platform for the rapid assembly of densely functionalized cyclopentenones from renewable furan feedstocks. This Perspective highlights recent advances in four key directions: enantioselective catalysis, cascade processes for polycyclic scaffolds, biomass valorization, and expanded heterocyclic variants. Chiral Brønsted acid catalysis, frequently paired with photoredox or transition-metal cocatalysis, now delivers highly enantio- and diastereoselective aza- and oxa-Piancatelli rearrangements, including three-component radical-mediated couplings that install diverse functionality in a single step. Strategic merger of the rearrangement with downstream Diels–Alder, hydroamination, or Friedel–Crafts reactions provides efficient access to complex polycyclic frameworks bearing multiple contiguous stereocenters. Parallel efforts have transformed 5-hydroxymethylfurfural (HMF) and 5-azidomethylfurfural (AMF) derivatives into bioactive cyclopentenones under sustainable and scalable conditions. Finally, the first interrupted aza-Piancatelli rearrangement on pyrrole substrates has extended the transformation beyond furans, enabling new amino Stenhouse photoswitches. These developments underscore the enduring synthetic power of the Piancatelli rearrangement and point to exciting opportunities in asymmetric complex-molecule synthesis, functional molecular materials, and expanded heterocyclic reaction development.