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Unified Approach to the Chemoselective ?-Functionalization of Amides with Heteroatom Nucleophiles.

ABSTRACT: Functionalization at the ?-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 ?-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 ?-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.

SUBMITTER: Goncalves CR

PROVIDER: S-EPMC6879173 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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

Gonçalves Carlos R CR Lemmerer Miran M Teskey Christopher J CJ Adler Pauline P Kaiser Daniel D Maryasin Boris B González Leticia L Maulide Nuno N

Journal of the American Chemical Society 20191112 46

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 6 ...[more]

PMID: 31714077

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