Palladium(II)-Catalyzed Alkene Functionalization via Nucleopalladation: Stereochemical Pathways and Enantioselective Catalytic Applications

Palladium(II)-catalyzed alkene functionalization via nucleopalladation through stereochemical pathways and enantioselective catalytic applications is studied. The oxidative cyclization of ortho-allyl phenols for the synthesis of dihydrobenzofurans was first reported in 1975 by Hosokawa and co-workers. A number of chiral catalysts were developed for enantioselective catalysis. Hayashi and co-workers employed a stereospecifically deuterated substrate to probe the mechanism of oxypalladation. Phenol cis-3-d-6 was subjected to Pd(MeCN)4(BF4)2, chiral ligand 7a, and the oxidant, benzoquinone in methanol. Oxypalladation involving alkene insertion into the phenol oxygen-Pd bond forms Pd-alkyl intermediate A. Stoltz and co-workers probed the stereochemical pathway of a similar oxypalladation reaction using a carboxylic acid substrate with a catalytic system capable of direct dioxygen-coupled turnover.