Direct α-Cross-Coupling of Benzylamines with Bulky Alkyl Iodides Enabled by Radical Carbonyl Catalysis

alpha-Amino radicals are highly reactive and synthetically valuable species. However, their instability and short lifetime limit their applications in organic synthesis. This work has demonstrated a catalytic strategy for in situ generation of persistent alpha-amino radicals from primary amines without protection of the NH2 group. In the presence of a carbonyl catalyst, primary amines could be converted into imines, which underwent deprotection and subsequent single electron transfer (SET) to produce resonancestabilized alpha-imino radicals. The persistent alpha-imino radicals underwent cross-coupling with another carbon radical or addition toward pi-systems, enabling new and challenging transformations that were not readily achievable through ionic pathways. By employing this strategy, we achieved direct alpha-cross-coupling of NH2-unprotected benzylamines and sterically hindered alkyl iodides with pyridoxal as the catalyst, producing a diverse array of bulky alpha-branched benzyl alkylamines and cyclic amines in good yields. The reaction mechanism involved SET and radical/radical coupling processes, demonstrating the process of radical carbonyl catalysis for the first time.