AI Article Synopsis
- * The study presents a novel method using dual photoredox/nickel catalysis to create tertiary alkylamines from organohalides and secondary alkylamines, via α-amino radicals and iminium ions.
- * This approach also allows for complex four-component reactions and can produce enantioenriched compounds, providing a promising route for synthesizing diverse tertiary amines.
Article Abstract
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 α-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- and sp-hybridized) in combination with secondary alkylamines and aldehydes. The multicomponent process proceeds through selective generation of α-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 α-aryl-substituted γ-amino acid derivatives. Taken together, this work offers a streamlined synthetic route to aliphatic tertiary amines.
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