Ruthenium-catalyzed three-component tandem remote C–H functionalization of naphthalenes: modular and concise synthesis of multifunctional naphthalenes†

Abstract

The prevalence of naphthalene compounds in biologically active natural products, organic ligands and approved drugs has motivated investigators to develop efficient strategies for their selective synthesis. C–H functionalization of naphthalene has been frequently deployed, but mainly involves two-component reactions, while multiple-component C–H functionalization for the synthesis of naphthalene compounds has thus far proven elusive. Herein, we disclose a versatile three-component protocol for the modular synthesis of multifunctional naphthalenes from readily available simple naphthalenes, olefins and alkyl bromides via P(III)-assisted ruthenium-catalyzed remote C–H functionalization. This protocol not only tolerates various functional groups, but can be applied to many natural product and drug derivatives, and can involve a three-component reaction with two different bioactive molecules. Mechanism studies indicated that the utilization of tertiary phosphines as auxiliary groups is the key to achieving the three-component free-radical reaction.