Ligand-enabled Z-retentive Tsuji-Trost reaction

Abstract

The palladium-catalyzed allylic substitution (Tsuji-Trost) reaction is widely applied in organic synthesis, especially for the synthesis of stereochemically well-defined olefins. However, the synthesis of Z-olefins via the Tsuji-Trost reaction has been challenging due to the thermodynamic instability of the corresponding anti-π-allyl-palladium intermediate. Here, we report a ligand-enabled palladium-catalyzed Z-retentive allylic substitution reaction that retains Z-olefin geometries. Palladium catalysts derived from sterically bulky phosphoramidite ligands well differentiate the reaction rates between the nucleophilic attack step and the π-σ-π isomerization process. The Z-retentive allylic substitution results from the nucleophilic attack occurring much faster than the isomerization process. The isomerization of anti-π-allyl-palladium intermediate into its syn-counterpart has been observed at a low temperature. These results provide a prospective approach for the preparation of chiral Z-olefin compounds.