Redox-Neutral Umpolung\nSynthesis of α‑Functionalized\nAmides

α-Heteroatom-substituted amides are useful as both\ntargets\nand intermediates but are challenging to synthesize via conventional\nenolate chemistry. Herein, we describe a general and unified umpolung\nprocedure to prepare α-heteroatom-functionalized secondary amides\nwith various heteroatom-based nucleophiles under redox-neutral conditions.\nThis transformation is a formal oxidation state reshuffle process\nfrom −N to −C in the hydroxamate, thereby achieving\nthe umpolung α-heterofunctionalization of carbonyl groups without\nexternal oxidants. Regulated by the reshuffle mechanism, functionalization\nexclusively occurs at the α-position of the hydroxamate and\nprecisely affords the α-functionalized amide with reliable predictability\neven in complex settings. Density functional theory studies support\nthat soft enolization enabled by Mg<sup>2+</sup>/DIPEA combination\nis essential to facilitate the formation of the α-lactam intermediate.\nThis represents the first general protocol to prepare α-functionalized\nsecondary amides.