Redox-Neutral Umpolung Synthesis of α-Functionalized Amides
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<sup>2+</sup>/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.
Authors
- Yuan‐Ye Jiang (ORCID: https://orcid.org/0000-0002-4763-9173)
- Rui Wang
- Wenbo Liu (ORCID: https://orcid.org/0000-0001-8442-2697)
- Shaokang An
- Yi-Xuan Xin (ORCID: https://orcid.org/0009-0002-9788-6970)
Institutions
- Sun Yat-sen University (CN)
- Qufu Normal University (CN)
Publication Details
- Journal
- JACS Au
- Published
- 2024-10-26
- DOI
- https://doi.org/10.1021/jacsau.4c00767
- Citations
- 8
- Primary Topic
- Advanced Synthetic Organic Chemistry
- Type
- article
- Field-Weighted Citation Impact
- 2.00
Funders
- Qufu Normal University
- National Natural Science Foundation of China
- Sun Yat-sen University
- Basic and Applied Basic Research Foundation of Guangdong Province