Palladium-catalyzed enantioselective β-hydride elimination for the construction of remote stereocenters

Abstract

The β-H elimination is a crucial elementary step in transition-metal catalysis, but controlling the stereochemistry of this process has been underdeveloped. The limited works reported so far have only focused on creating axial chirality in allenes, and no report has been able to build central chirality using asymmetric β-H elimination. In this study, we report a Trost ligand-enabled enantioselective desymmetric β-H elimination reaction from π-allyl-Pd. This transformation provides rapid access to cyclohexenes bearing a C4-remoted stereocenter, and total synthesis of (-)-oleuropeic acid and (-)-7-hydroxyterpineol is demonstrated. Computational studies have shown that the β-H elimination is the rate-determining step, and the non-covalent interactions between the amide moiety of the Trost ligand and the benzene and cyclohexane moieties of the substrate play a key role in stereocontrol during the β-H elimination.