Oxidative rearrangement of 1,1-disubstituted alkenes to ketones

The Wacker process, which is widely used to convert monosubstituted alkenes into the corresponding methyl ketones, is thought to proceed through a Pd^II/Pd⁰ catalytic cycle involving a β-hydride elimination step. This mechanistic scenario is inapplicable to the synthesis of ketones from the 1,1-disubstituted alkenes. Current approaches based on semi-pinacol rearrangement of Pd^II intermediates are limited to the ring expansion of highly strained methylene cyclobutane derivatives. Herein, we report a solution to this synthetic challenge by designing a Pd^II/Pd^IV catalytic cycle incorporating a 1,2-alkyl/Pd^IV dyotropic rearrangement as a key step. This reaction, compatible with a broad range of functional groups, is applicable to both linear olefins and methylene cycloalkanes, including macrocycles. Regioselectivity favors the migration of the more substituted carbon, and a strong directing effect of the β-carboxyl group was also observed.