Directed nickel-catalyzed regio- and diastereoselective arylamination of unactivated alkenes

Few methods exist to add a carbon and nitrogen atom across an unfunctionalized alkene. Here the authors show a method to regio- and diastereoselectively add aryl and amino groups to terminal and internal alkenes, via nickel catalysis and a removable directing group. Few methods have been reported for intermolecular arylamination of alkenes, which could provide direct access to important arylethylamine scaffolds. Herein, we report an intermolecular syn-1,2-arylamination of unactivated alkenes with arylboronic acids and O-benzoylhydroxylamine electrophiles with Ni(II) catalyst. The cleavable bidentate picolinamide directing group facilitates formation of stabilized 4-, 5- or 6-membered nickelacycles and enables the difunctionalization of diverse alkenyl amines with high levels of regio-, chemo- and diastereocontrol. This general and practical protocol is compatible with broad substrate scope and high functional group tolerance. The utility of this method is further demonstrated by the site-selective modification of pharmaceutical agents.

Automated summary

The authors presented a method to add aryl and amino groups to alkenes regio- and diastereoselectively via nickel catalysis and a removable directing group. This method enables high levels of regio-, chemo- and diastereocontrol, and is compatible with broad substrate scope and high functional group tolerance. The utility of this method in site-selective modification of pharmaceutical agents has been demonstrated.