Copper-Catalyzed Enantioselective Hydroboration of 1,1-Disubstituted Alkenes: Method Development, Applications and Mechanistic Studies

Cu-catalyzed enantioselective Cu-B(pin) addition to 1,1-disubstituted alkenes generating tertiary alkylcopper complexes that contain a quaternary stereogenic center, followed by the protonation of the complexes are presented. The resulting formal hydroboration products are formed in up to 98% yield and 99:1 enantiomeric ratio. The C-B(pin) moiety can be converted to a variety of useful functional groups. The method is applied to the enantioselective formal synthesis of (R)-ketoprofen. Detailed stereochemical models for enantioselective induction were elucidated through DFT calculations.