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

ABSTRACT 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.