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Oxidative rearrangement of 1,1-disubstituted alkenes to ketones

Qiang Feng, Qian Wang, Jieping Zhu

2023Science64 citationsDOIOpen Access PDF

Abstract

The Wacker process, which is widely used to convert monosubstituted alkenes into the corresponding methyl ketones, is thought to proceed through a Pd II /Pd 0 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.

Topics & Concepts

ChemistryRegioselectivityMethyleneCatalytic cycleCyclobutaneAlkylCatalysisRing (chemistry)Oxidative additionMedicinal chemistryHydrideCombinatorial chemistryPhotochemistryOrganic chemistryHydrogenCatalytic C–H Functionalization MethodsOxidative Organic Chemistry ReactionsCatalytic Alkyne Reactions
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