Intermolecular Asymmetric Arylative Dearomatization of 1-Naphthols.

Abstract

Arylative dearomatization forms quaternary stereocenters in cyclic systems with the concomitant introduction of an aromatic ring. Pd-catalyzed arylative dearomatization, which uses conditions analogous to cross-coupling, has emerged as a powerful method in an intramolecular context. But translating this from intramolecular cyclizations to an intermolecular process has proven extremely challenging: examples are scarce, and those that exist have not been rendered enantioselective, despite the potential for broad application in medicinal chemistry and natural product synthesis. We describe a strategy that utilizes attractive interactions between the ligand and substrate to overcome this challenge and promote intermolecular, highly enantioselective arylative dearomatization of naphthols using a broad range of aryl bromide electrophiles. Crucial to success is the use of the readily accessed sulfonated chiral phosphine sSPhos, which we believe engages in attractive electrostatic interactions with the substrate. Not only does sSPhos control enantioselectivity but it also drastically accelerates the reaction, most likely by facilitating the challenging palladation step that initiates dearomatization.