Transition‐Metal‐Free Reductive Functionalization of Tertiary Carboxamides and Lactams for α‐Branched Amine Synthesis

A new method for the synthesis of α‐branched amines by reductive functionalization of tertiary carboxamides and lactams is described. The process relies on the efficient and controlled reduction of tertiary amides by a sodium hydride/sodium iodide composite, in situ treatment of the resulting anionic hemiaminal with trimethylsilyl chloride and subsequent coupling with nucleophilic reagents including Grignard reagents and tetrabutylammonium cyanide. The new method exhibits broad functional‐group compatibility, operates under transition‐metal‐free reaction conditions, and is suitable for various synthetic applications on both sub‐millimole and on multigram scales. A transition‐metal‐free method for the synthesis of α‐branched amines from tertiary carboxamides and lactams with carbon‐centered nucleophiles has been developed. This scalable process relies on the controlled reduction of tertiary amides by NaH/NaI composite, in situ treatment of the resulting anionic hemiaminal with trimethylsilyl chloride, and subsequent coupling with nucleophilic reagents including Grignard reagents and tetrabutylammonium cyanide.