PdII-Catalyzed C(alkenyl)-H Activation Facilitated by a Transient Directing Group

Palladium(II)-catalyzed C(alkenyl)-H alkenylation enabled by a transient directing group (TDG) strategy is described. The dual catalytic process takes advantage of reversible condensation between an alkenyl aldehyde substrate and an amino acid TDG to facilitate coordination of the metal catalyst and subsequent C(alkenyl)-H activation by a tailored carboxylate base. The resulting palladacycle then engages an acceptor alkene, furnishing a 1,3-diene with high regio- and E/Z-selectivity. The reaction enables the synthesis of enantioenriched atropoisomeric 2-aryl-substituted 1,3-dienes, which have seldom been examined in previous literature. Catalytically relevant alkenyl palladacycles were synthesized and characterized by X-ray crystallography, and the energy profiles of the C(alkenyl)-H activation step and the stereoinduction model were elucidated by density functional theory (DFT) calculations.

Automated summary

This paper describes a palladium(II)-catalyzed C(alkenyl)-H alkenylation reaction enabled by a transient directing group strategy. The reaction takes advantage of reversible condensation between the substrate and a transient directing group to facilitate the coordination of the metal catalyst and subsequent activation of the C(alkenyl)-H bond. The reaction produces 1,3-dienes with high regio- and E/Z-selectivity and enables the synthesis of enantioenriched atropoisomeric 2-aryl-substituted 1,3-dienes that have seldom been studied before. The reaction mechanism and stereoinduction model were elucidated by density functional theory calculations and the alkenyl palladacycles were characterized by X-ray crystallography.