Quaternary Carbon Editing Enabled by Sequential Palladium Migration

Peripheral functionalization of a quaternary carbon via C(sp³)-H bond activation has made significant progress in recent years. However, direct editing of a quaternary carbon through Csp³-Csp³ bond cleavage and refunctionalization of nonstrained acyclic molecules remain underexploited. Herein we report a reaction in which a methyl group attached to a quaternary carbon is shifted to its neighboring secondary carbon with concurrent oxidation of the quaternary C-C single bond to the C═C double bond. Specifically, morpholinyl amide of 2,2-dimethyl alkanoic acids is converted to 2-methylene-3-methyl alkanoic acid derivatives in the presence of a catalytic amount of palladium acetate, Selectfluor and sodium carbonate. Control experiments suggest that the reaction proceeds via a sequence of selective C(sp³)-H activation of the methyl group, oxidation of the resulting C(sp³)-Pd^II to Pd^IV intermediate followed by unprecedented 1,3-Pd^IV migration, 1,2-methyl/Pd^IV dyotropic rearrangement and finally, β-Hydride elimination. In this domino process, palladium migrates successively from the primary to the secondary and finally to the quaternary carbon, leading to the concurrent functionalization of a primary, a secondary, and a quaternary carbon.