Unified Approach to the Chemoselective α‑Functionalization of Amides with Heteroatom Nucleophiles

Functionalization at the α-position of carbonyl compounds has classically relied on enolate chemistry. As a result, the generation of a new C–X bond, where X is more electronegative than carbon requires an oxidation event. Herein we show that, by rendering the α-position of amides electrophilic thro...

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Bibliographic Details
Published in:Journal of the American Chemical Society 2019-11, Vol.141 (46), p.18437-18443
Main Authors: Gonçalves, Carlos R, Lemmerer, Miran, Teskey, Christopher J, Adler, Pauline, Kaiser, Daniel, Maryasin, Boris, González, Leticia, Maulide, Nuno
Format: Article
Language:English
Subjects:
Chemical Sciences
Organic chemistry
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Summary:Functionalization at the α-position of carbonyl compounds has classically relied on enolate chemistry. As a result, the generation of a new C–X bond, where X is more electronegative than carbon requires an oxidation event. Herein we show that, by rendering the α-position of amides electrophilic through a mild and chemoselective umpolung transformation, a broad range of widely available oxygen, nitrogen, sulfur, and halogen nucleophiles can be used to generate α-functionalized amides. More than 60 examples are presented to establish the generality of this process, and calculations of the mechanistic aspects underline a fragmentation pathway that accounts for the broadness of this methodology.
ISSN:0002-7863
1520-5126
DOI:10.1021/jacs.9b06956