Quaternary Carbon Editing Enabled by Sequential Palladium Migration
Hua Wu, Takuji Fujii, Qian Wang, Jieping Zhu
Abstract
Peripheral functionalization of a quaternary carbon via C(sp 3 )–H bond activation has made significant progress in recent years. However, direct editing of a quaternary carbon through Csp 3 –Csp 3 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(sp 3 )–H activation of the methyl group, oxidation of the resulting C(sp 3 )–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.