One-pot ruthenium-catalyzed synthesis of benzyl/allyl-halide substituted (dihydro)naphthalenes via radical benzannulation

We report a unique one-pot synthetic route to reactive benzyl- and allyl-halide-substituted naphthalenes and dihydronaphthalenes from 2,3-aryl-1,3-butadiene substrates and halogenated alkanes with [Cp*RuCl(PPh3)2], a commercially available catalyst. The reaction is tolerant to various functional groups, including reactive carbonyl groups, halides, and trimethylsilyl groups. The scope of catalytic reactions was expanded to include a heteroaromatic thiophene ring system, demonstrating full regioselectivity toward the benzo[b]thiophene product. The resulting (dihydro-)naphthalene products are relevant synthons for drug synthesis, allowing for facile post-functionalization by making use of the reactive (benzylic or allylic) halide functionalities. Mechanistic studies were combined with DFT, which revealed a sequential catalytic ATRA, radical benzannulation, and HCl elimination sequence. The initial ATRA step results in a 1,4-addition intermediate that subsequently undergoes a 6-endo-trig cyclization via a radical addition on the pendant arene. This cyclized intermediate subsequently undergoes HCl elimination to generate benzyl- and allyl-halide substituted (dihydro-)naphthalenes.