Modular functionalization of arenes in a triply selective sequence: rapid C(sp²) and C(sp³) coupling of C−Br, C−OTf, and C−Cl bonds enabled by a single palladium(I) dimer

Full control over multiple competing coupling sites would enable straightforward access to densely functionalized compound libraries. Historically, the site selection in Pd⁰-catalyzed functionalizations of poly(pseudo)halogenated arenes has been unpredictable, being dependent on the employed catalyst, the reaction conditions, and the substrate itself. Building on our previous report of C−Br-selective functionalization in the presence of C−OTf and C−Cl bonds, we herein complete the sequence and demonstrate the first general arylations and alkylations of C−OTf bonds (in <10 min), followed by functionalization of the C−Cl site (in <25 min), at room temperature using the same air- and moisture-stable Pd^I dimer. This allowed the realization of the first general and triply selective sequential C−C coupling (in 2D and 3D space) of C−Br followed by C−OTf and then C−Cl bonds.