Catalytic Asymmetric Radical-Mediated Three-Component Piancatelli-Type Rearrangement of Furylalkenes

As one of the most fundamental rearrangement reactions, the classical Piancatelli reaction mainly relies on the use of α-furylcarbinols and is initiated by an acid-promoted dehydroxylation process and limited to a two-component manner. In this work, the first asymmetric radical-mediated three-component Piancatelli-type rearrangement of furylalkenes with diverse carbon-centered radical precursors and anilines is developed via the combination of copper­(I) or photoredox catalysis with chiral Brønsted acid and unchiral Lewis acid catalysis. This protocol features a wide substrate scope and high functional group tolerance and provides expedient access toward a broad spectrum of densely functionalized fluoroalkyl-containing cyclopentenones bearing α-quaternary carbon stereocenters in high yields with high enantioselectivities and diastereoselectivities (>70 examples, up to 95% yield, 96% ee, and >20/1 dr). The synthetic utility has been demonstrated by product derivations and applying onto the late-stage functionalization of valuable drug targets or natural products. Mechanistic studies revealed that the diastereoselectivity of the rearrangement reaction was controlled by Dy­(III)-accelerated Z/E isomerization of the Piancatelli intermediates and the chiral Brønsted acid-catalyzed 4π-electrocyclization of pentadienyl carbocation intermediates was both a rate- and enantio-determining step.