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Aminative Suzuki-Miyaura Coupling: Tackling Alkyl Nucleophiles and Addressing the Viability of the Electrophile-First
1Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford St., Cambridge, MA, 02138, USA.
Abstract:
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).
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