Palladium-Catalyzed γ-Selective and Stereospecific Allyl−Aryl Coupling between Acyclic Allylic Esters and Arylboronic Acids

Reactions between acyclic ( E )-allylic acetates and arylboronic acids in the presence of a palladium catalyst prepared from Pd(OAc) 2, phenanthroline (or bipyridine), and AgSbF 6 (1:1.2:1) proceeded with excellent γ-selectivity to afford allyl−aryl coupling products with E -configuration. The reactions of α-chiral allylic acetates took place with excellent α-to-γ chirality transfer with syn stereochemistry to give allylated arenes with a stereogenic center at the benzylic position. The reaction tolerated a broad range of functional groups in both the allylic acetates and the arylboronic acids. Furthermore, γ-arylation of cinnamyl alcohol derivatives afforded gem- diarylalkane derivatives containing an unconjugated alkenic substituent. The synthetic utility of this method was demonstrated by its utilization in an efficient synthesis of (+)-sertraline, an antidepressant agent. The observed γ-regioselectivity and E -1,3- syn stereochemistry were rationalized based on a Pd(II) mechanism involving transmetalation between a cationic mono(acyloxo)palladium(II) complex and arylboronic acid, and directed carbopalladation followed by syn -β-acyloxy elimination. The results of stoichiometric reactions of palladium complexes related to possible intermediates were fully consistent with the proposed mechanism.