General acid-mediated aminolactone formation using unactivated alkenes

Abstract

Spirocyclic butyrolactones and butenolides are widespread structural motifs in bioactive substances. Despite their prevalence, a simple method ensuring their direct preparation from exocyclic alkenes, ideally in a late-stage context, remains elusive. Herein, we report direct aminolactone formation using unactivated alkenes which addresses this gap, employing cheap and readily available reactants. The method relies on the hijacking of a cationic aminoalkylation pathway and affords (spiro)aminolactones with excellent functional group tolerance and chemoselectivity. The synthetic versatility of the products is demonstrated through a range of transformations, notably exploiting stereospecific rearrangement chemistry to produce sterically congested scaffolds.