Z-Retentive Enantioselective Rh-Catalyzed Hydroarylation of E,Z-Dienes

Metal-catalyzed additions to alkenes are among the most versatile methods to prepare enantioenriched small molecules. Processes that selectivity functionalize an E-alkene in the presence of a Z-alkene remain elusive, however, they would be an attractive approach to access chiral molecules with a remaining group capable of stereospecific functionalization. Here, we report the Z-retentive enantioselective Rh-catalyzed hydroarylation of electron-poor E,Z-dienes. The reaction gives targets in >95% ee without alkene Z-to-E isomerization. The product β-aryl-Z-γ,δ-unsaturated carbonyl compounds can be readily transformed into polyfunctional products containing multiple adjacent stereocenters in high diastereomeric ratios (≥90:10) via stereospecific alkene functionalizations. Mechanistic studies suggest that Rh-enolate protonolysis is the turnover-limiting step, and a selectivity model is developed based on reactivity and kinetic studies with E,E-dienes and E/Z-alkenes. DFT studies were used to shed light on the nature of the substrate-catalyst interactions which likely lead to the observed selectivity. These results may have wide spanning implications for developing new Z-retentive alkene addition reactions.