All-Carbon Quaternary Stereogenic Centers by Enantioselective Cu-Catalyzed Conjugate Additions Promoted by a Chiral N-Heterocyclic Carbene

摘要

The design of new chiral catalysts for enantioselective synthesis of all-carbon quaternary stereogenic centers is a critical and challenging objective in modern chemistry.[1] Such catalysts must be enantio-differentiating but also especially active because the desired reactions involve additions of carbon nucleophiles to sterically congested electrophilic sites. Herein, we disclose a readily available chiral N-heterocyclic carbene (NHC) that can be used to promote the catalytic asymmetric conjugate addition (ACA)[2] of organozinc reagents to cyclicγ-keto esters [Eq. (1)]; these transformations give rise to the enantioselective formation of all-carbon quaternary stereogenic centers that bear a readily functionalizable carboxylic ester substituent in up to 95 % ee.[3]-[5] In nearly all of the catalytic ACA reactions (one exception), the new chiral NHC (Cu complex generated in situ) delivers significantly higher efficiency and asymmetric induction than the previously reported systems.