Enantioselective Preparation of Arenes with β-Stereogenic Centers: Confronting the 1,1-Disubstituted Olefin Problem Using CuH/Pd Cooperative Catalysis.

Arenes with β-stereogenic centers are important substructures in pharmaceuticals and natural products. We have developed an asymmetric anti-Markovnikov hydroarylation of 1,1-disubstituted olefins by dual palladium and copper hydride catalysis as a convenient and general approach to access these substructures. This efficient one-step process addresses several limitations of the traditional stepwise approaches. The use of cesium benzoate as a base and a common phosphine ligand for both the Cu- and Pd-catalyzed processes were important discoveries that allow these challenging olefin substrates to be efficiently transformed. A variety of aryl bromide coupling partners, including numerous heterocycles, were coupled with 1,1-disubstituted alkenes to generate arenes with β-stereogenic centers.