Multicomponent Construction of Tertiary Alkylamines by Photoredox/Nickel-Catalyzed Aminoalkylation of Organohalides

Tertiary alkylamines are privileged structural motifs widely present in natural products, pharmaceutical agents, and bioactive molecules, and their efficient synthesis has been a longstanding goal in organic chemistry. The functionalization of alpha-amino radicals derived from abundant precursors represents an emerging approach to accessing alkylamines, but application of this strategy to obtain tertiary alkylamines remains challenging. Here, we show that dual photoredox/nickel catalysis enables aminoalkylation of organohalides (sp(2)- and sp(3)-hybridized) in combination with secondary alkylamines and aldehydes. The multicomponent process proceeds through selective generation of alpha-amino radicals from the reduction of in situ-generated iminium ions by photoredox catalysis, followed by nickel-catalyzed cross-coupling to build a wide array of functionally diverse tertiary alkylamines. This strategy could also be extended to unprecedented four-component reactions and their asymmetric variants to deliver enantioenriched alpha-aryl-substituted gamma-amino acid derivatives. Taken together, this work offers a streamlined synthetic route to aliphatic tertiary amines.