Catalytic Asymmetric Radical-Mediated Three-Component Piancatelli-Type Rearrangement of Furylalkenes
Lei Xu, Sishi Zhong, Qian Yang, Jie Wei, Jiaming Zou, Hongxiang Li, Yunfei Cai
Abstract
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.