Intermolecular\nAsymmetric Arylative Dearomatization\nof 1‑Naphthols

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