Atom transfer radical addition on aromatic rings: Ruthenium-catalyzed synthesis of benzyl/allyl-halide substituted (dihydro)naphthalenes

We report the first example of aromatic atom transfer radical cyclization (ArATRC)—involving an intramolecular atom transfer radical addition (ATRA) onto an aromatic system—by utilizing a [Cp*RuCl(PPh3)2] catalyst at room temperature. The reaction of 2,3-aryl-1,3-butadiene substrates with halogenated alkanes proceeds via sequential ATRA, atom transfer radical cyclization (ATRC) and HCl elimination, yielding benzyl- and allyl-halide substituted naphthalenes and dihydronaphthalenes with various functional groups, including reactive carbonyls, halides, and trimethylsilyl. The scope of catalytic reactions was expanded to include a heteroaromatic thiophene ring system demonstrating full regioselectivity toward the benzo[b]thiophene product. Mechanistic studies were combined with DFT to reveal sequential catalytic ATRA and ArATRC steps. The ATRA step yields a 1,4-addition intermediate that subsequently undergoes a radical 6-endo-trig cyclization, formally representing an ArATRC reaction. The resulting products demonstrate utility as relevant synthons in drug synthesis, allowing for facile post-functionalization by making use of reactive (benzylic) halide functionalities.