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Ligand-Enabled ?-C(sp3)-H Activation of Ketones.

ABSTRACT: We report the first example of Pd(II)-catalyzed ?-C(sp3)-H activation of ketones directed by a practical 2,2-dimethyl aminooxyacetic acid auxiliary. 2-Pyridone ligands are identified to enable C(sp3)-H activation for the first time. A rare six-membered palladacycle intermediate is isolated and characterized to elucidate the reaction mechanism. Both (hetero)arylation and vinylation of ?-C(sp3)-H bonds are demonstrated. Sequential ?- and ?-C(sp3)-H (hetero)arylation of muscone showcases the utility of this method for late-stage diversification. A convenient Mn(II)-catalyzed auxiliary removal is also developed to further underscore the practicality of this transformation.

SUBMITTER: Zhu RY

PROVIDER: S-EPMC5851877 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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Ligand-Enabled γ-C(sp3)-H Activation of Ketones.

Zhu Ru-Yi RY Li Zi-Qi ZQ Park Han Seul HS Senanayake Chris H CH Yu Jin-Quan JQ

Journal of the American Chemical Society 20180302 10

We report the first example of Pd(II)-catalyzed γ-C(sp3)-H activation of ketones directed by a practical 2,2-dimethyl aminooxyacetic acid auxiliary. 2-Pyridone ligands are identified to enable C(sp3)-H activation for the first time. A rare six-membered palladacycle intermediate is isolated and characterized to elucidate the reaction mechanism. Both (hetero)arylation and vinylation of γ-C(sp3)-H bonds are demonstrated. Sequential β- and γ-C(sp3)-H (hete ...[more]

PMID: 29481072

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