Dearomative 1,4-difunctionalization of naphthalenes via palladium-catalyzed tandem Heck/Suzuki coupling reaction.

Abstract

Dearomative functionalization reactions represent an important strategy for the synthesis of valuable three-dimensional molecules from simple planar aromatics. Naphthalene is a challenging arene towards transition-metal-catalyzed dearomative difunctionalization reactions. Reported herein is an application of naphthalene as a masked conjugated diene in a palladium-catalyzed dearomative 1,4-diarylation or 1,4-vinylarylation reaction via tandem Heck/Suzuki sequence. Three types of 1,4-dihydronaphthalene-based spirocyclic compounds are achieved in excellent regio- and diastereoselectivities. Key to this transformation is the inhibition of a few competitive side reactions, including intramolecular naphthalenyl C-H arylation, intermolecular Suzuki cross-coupling, dearomative 1,2-difunctionalization, and dearomative reductive-Heck reaction. Density functional theory (DFT) calculations imply that the facile exergonic dearomative insertion of a naphthalene double bond disrupts the sequence of direct Suzuki coupling, leading to the tandem Heck/Suzuki coupling reaction. The observed regioselectivity towards 1,4-difunctionalization is due to the steric repulsions between the introduced aryl group and the spiro-scaffold in 1,2-difunctionalization.