Aminative Suzuki–Miyaura Coupling: Tackling Alkyl Nucleophiles and Addressing the Viability of the Electrophile‐First Mechanism

Insertive cross-coupling reactions provide the option of repurposing widely available coupling partners for the formation of new linkages. By confronting a major limitation of the aminative Suzuki-Miyaura methods we recently reported, we achieve a general method for the Pd-catalyzed aminative coupling of primary and secondary alkyl boronic esters with aryl (pseudo)halides. Introducing a formal nitrene insertion into this Suzuki-Miyaura reaction diverts the outcome from the traditional C(sp²)─C(sp³) products to the C(sp²)─NH─C(sp³) analogues (N-aryl anilines). DFT calculations and experimental mechanistic studies indicate that C─N bond formation from the electrophilic aryl component occurs first, providing further evidence for this previously hypothetical pathway. By comparison of several transition state structures, we find that C─N bond formation likely takes place through an unusual dyotropic rearrangement of a LPd(Ar)NHX complex (X = OPOPh₂).