Gold(I)-Catalyzed Asymmetric Transformations of 1-(1-Alkynyl)cyclobutyl Ketones: Access to Enantioenriched Cyclopenta[ b ]furans Bearing Vicinal Bridged Quaternary Stereocenters

Abstract

Present herein is a gold(I)-catalyzed asymmetric cascade reaction of 1-(1-alkynyl)cyclobutyl ketones. Upon activation by a chiral phosphoric-acid-tethered gold(I) complex, they undertake intramolecular 5-endo-dig cyclization, and the resulting oxocarbenium species engage in an asymmetric 1,2-alkyl migration to generate gold-containing cyclopenta[b]furan carbocations, which can be intercepted by a broad range of nucleophiles, including indoles, pyrroles, alcohols, and amines, providing efficient access to synthetically challenging tetrahydro-4H-cyclopenta[b]furans bearing vicinal bridged quaternary stereocenters with fair to high enantioselectivity. The intermediates can also participate in (3 + 2) annulations with suitable 1,3-dipoles to afford polycyclic architectures with high molecular complexity. Mechanistic studies and density function theory calculations elucidate the key factors governing the catalytic pathways and stereochemical outcomes.