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.