Assisted Tandem Pd Catalysis Enables Regiodivergent Heck Arylation of Transiently Generated Substituted Enol Ethers

[Image: see text] Two complementary regiodivergent Pd-catalyzed assisted tandem [isomerization/Heck arylation] reactions are reported. They provide access to a broad array of acyclic trisubstituted vinyl ethers starting from readily available alkenyl ethers. In both cases, the isomerization is conducted with a [Pd–H] precatalyst supported by tris-tert-butyl phosphine ligands. When the catalyst is modified by the addition of a chelating bisphosphine ligand (dppp), an organic base (Cy(2)NMe), sodium acetate, and aryl triflates are used as electrophiles, the α-arylation pathway is promoted preferentially. The β-arylation pathway is favored for electron-deficient and electron-neutral aryl halides when the catalyst is simply modified by the addition of an excess of an organic base (Et(3)N) after completion of the isomerization reaction. Electron-rich aryl halides lead to reduced levels of regiocontrol. The moderate stereoselectivity obtained are proposed to reflect the absence of stereocontrol in the isomerization step. Computational analyses suggest that migratory insertion is selectivity-determining for both the arylations. For the β-selective arylation, an energy decomposition analysis underscored that electronic factors favor α-regioselectivity and steric effects favor β-regioselectivity. Preliminary investigations show that high levels of stereoselectivity can be achieved for the α-selective arylation by ligand control. Complementarily, reaction conditions for postcatalytic stereo-correction have also been identified for each catalytic system.