Modular Synthesis of alpha-Branched Secondary Alkylamines via Visible-light-mediated Carbonyl Alkylative Amination

The development of methods for the assembly of alpha-branched secondary alkylamines remains a central challenge to chemical synthesis because of their critical importance in modulating the physical properties of biologically active molecules. Despite decades of intensive research, chemists still rely on selective N-alkylation and carbonyl reductive amination to make most amine products. Here we report the further evolution of a carbonyl alkylative amination process that, for the first time, brings together primary amines, aldehydes and alkyl iodides in a visible-light-mediated multicomponent coupling reaction for the synthesis of a wide range of -branched secondary alkylamines. In addition to exploring the structural tolerance and limitations in each reaction component, we also report preliminary applications to the telescoped synthesis of -branched N-heterocycles and a primary-selective N-alkylation protocol based on carbonyl alkylative amination. We believe that this method will enable practitioners of synthetic chemistry in academic and industrial settings to approach the synthesis of these important molecules in a manner that is distinct from established approaches.