Year: 2024
Type: article
Abstract: High Resolution Image Download MS PowerPoint Slide α-Heteroatom-substituted amides are useful as both targets and intermediates but are challenging to synthesize via conventional enolate chemistry. Herein, we describe a general and unified umpolung procedure to prepare α-heteroatom-functionalized secondary amides with various heteroatom-based nucleophiles under redox-neutral conditions. This transformation is a formal oxidation state reshuffle process from −N to −C in the hydroxamate, thereby achieving the umpolung α-heterofunctionalization of carbonyl groups without external oxidants. Regulated by the reshuffle mechanism, functionalization exclusively occurs at the α-position of the hydroxamate and precisely affords the α-functionalized amide with reliable predictability even in complex settings. Density functional theory studies support that soft enolization enabled by Mg 2+ /DIPEA combination is essential to facilitate the formation of the α-lactam intermediate. This represents the first general protocol to prepare α-functionalized secondary amides.
Source: JACS Au
Institutions: Sun Yat-sen University, Qufu Normal University
Language: English
Subfield: Organic Chemistry
Field: Chemistry
Domain: Physical Sciences
Open Access status: gold
Estimated APC paid: $3,500
Awards: G2804777362, G4035174606, G7470894867
OpenAlex ID: W4403789963