Silver-Catalyzed Asymmetric Double Desymmetrization via Vinylogous Michael Addition of Prochiral α,α-Dicyanoalkenes to Cyclopentendiones

An asymmetric double desymmetrization methodology has been developed for synthesizing densely functionalized chiral cyclopentylcyclohexane scaffolds. We have constructed four chiral centers, including an all-carbon quaternary stereocenter in a single C-C bond formation event. The methodology has high functional-group tolerance and delivers a broad range of enantioenriched products. This vinylogous Michael addition reaction of prochiral alpha,alpha-dicyanocyclohexane to 2,2-disubstituted cyclopentene-1,3-dione is catalyzed by a chiral Ag-(R)-DTBM-SEGPHOS catalyst. An asymmetric double desymmetrization reaction has been realized through vinylogous Michael addition reaction of prochiral alpha,alpha-dicyanocyclohexane to 2,2-disubstituted cyclopentene-1,3-dione catalyzed by a chiral Ag-(R)-DTBM-SEGPHOS catalyst. This method enables the formation of four chiral centers, including an all-carbon quaternary stereocenter in a single C-C bond formation event. image