Asymmetric Total Synthesis of Penicilfuranone A through NHC-Catalyzed Umpolung

The first asymmetric total synthesis of penicifuranone A was accomplished in eight steps through an NHC-catalyzed umpolung strategy. Key features of the synthesis include an Al-Salen catalyzed asymmetric cyanosilylation to install the tertiary alcohol of gregatin A, and an NHC catalyzed Stetter-Aldol cascade reaction. The umpolung strategy of the benzyl aldehyde fragment facilitated a convergent formal [4 + 2] annulation with gregatin A, ultimately leading to the formation of penicifuranone A.