Base-Controlled Dual Pd-Catalysis Enabling Tunable Tandem C(sp3 )-H Activation-Annulation and 6-endo-trig Heck Cyclization

Exploring the divergent reactivity of a common precursor to access a wide array of products has long been a central focus in synthetic organic chemistry. Substrates bearing multiple reactive sites often exhibit diverse reactivity profile, which can be selectively utilized through careful methodological design. Herein, we unveil a base-controlled, switchable dual reactivity of a palladium catalyst towards a designed haloarene substrate, enabling either a tandem C(sp 3)-H activation-annulation or a 6-endo-trig Heck reaction pathway. In this study, we show that by precisely adjusting the reaction conditions with the optimal combination of base and solvent in the presence of a single Pd catalyst/ligand, it is possible to direct the reaction to produce two different scaffolds simultaneously. Mechanistic studies suggest that C(sp 3 )-H activation promoted by an inorganic carbonate base is key to the formation of an exclusive arylnaphthalene scaffold, while the use of an organic amine base triggers a lesser-known intramolecular 6-endo-trig Heck reaction affording aryldihydronaphthalene motifs. This paper presents a concise, efficient, and tunable synthetic strategy for the synthesis of bioactive compounds from the lignan family, as well as other significant (hetero)polyarenes, naphthalenes, and anthracenes.