Ligand-Enabled γ-C(sp 3 )-H Activation of Ketones.

Authors :: Zhu RY
Li ZQ
Park HS
Senanayake CH
Yu JQ
Source :: Journal of the American Chemical Society [J Am Chem Soc] 2018 Mar 14; Vol. 140 (10), pp. 3564-3568. Date of Electronic Publication: 2018 Mar 02.
Publication Year :: 2018
Abstract: We report the first example of Pd(II)-catalyzed γ-C(sp <superscript>3</superscript> )-H activation of ketones directed by a practical 2,2-dimethyl aminooxyacetic acid auxiliary. 2-Pyridone ligands are identified to enable C(sp <superscript>3</superscript> )-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(sp <superscript>3</superscript> )-H bonds are demonstrated. Sequential β- and γ-C(sp <superscript>3</superscript> )-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.