Arenes with ?-stereogenic centers are important substructures in pharmaceuticals and natural products. Their synthesis traditionally involves two separate and individually challenging steps: enantioselective synthesis of a chiral main-group organometallic complex and subsequent cross-coupling with an aryl electrophile. We describe the development of asymmetric anti-Markovnikov hydroarylation of 1,1-disubstituted olefins by dual palladium and copper hydride catalysis as a convenient and significantly more general alternative. This reaction is an efficient one-step process that addresses several limitations of the 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 allowed these challenging olefin substrates to be efficiently transformed to products. A variety of aryl bromide coupling partners, including numerous heterocycles, were coupled with 1,1-disubstituted alkenes to generate arenes with ?-stereogenic centers. Finally, the effect of the level of olefin substitution on reaction yield and enantioselectivity has been investigated.
“The Enantioselective Preparation of Arenes with β-Stereogenic Centers: Confronting the 1,1-Disubstituted Olefin Problem Using CuH/Pd Cooperative Catalysis”, Angew. Chem. Int. Ed., 2020, https://doi.org/10.1002/anie.202004414.