Rapid Access to Densely Functionalized Cyclopentenyl Sulfoximines through a Sc-Catalyzed Aza-Piancatelli Reaction

Abstract

Sulfoximines make up a class of compounds of growing interest for crop science and medicinal chemistry, but methods for directly incorporating them into complex molecular scaffolds are lacking. Here we report a scandium-catalyzed variant of the aza-Piancatelli cyclization that can directly incorporate sulfoximines as nucleophiles rather than the classical aniline substrates. Starting from 2-furylcarbinols and sulfoximines, the reaction provides direct access to 4-sulfoximinocyclopentenones, a new scaffold bearing cyclopentenone and sulfoximine motifs, both of interest for bioactive compounds.

From 5-HMF to Novel Cyclopentenone-Based Aza Spirocycles: An Intramolecular Aza-Piancatelli Reaction in Action

“…While anilines were efficient nucleophiles, alkylamines remained unreactive under classical acidic conditions, and N,O -dialkyl-hydroxylamines were used as their masked nitrogen surrogates . While editing this manuscript, Lebœuf et al described sulfoximines as nucleophiles for a Sc­(OTf) 3 -catalyzed intermolecular aza-Piancatelli reaction …”