Catalytic Asymmetric Polycyclization of Tertiary Enamides with Silyl Enol Ethers: Total Synthesis of (-)-Cephalocyclidin A

J Am Chem Soc. 2023 Dec 13;145(49):26550-26556. doi: 10.1021/jacs.3c11178. Epub 2023 Nov 29.

Abstract

A catalytic enantioselective polycyclization of tertiary enamides with terminal silyl enol ethers has been developed by virtue of Cu(OTf)2 catalysis with a novel spiropyrroline-derived oxazole (SPDO) ligand. This tandem reaction offers an effective approach to assemble bicyclic and tricyclic N-heterocycles bearing both aza- and oxa-quaternary stereogenic centers, which are primal subunits in a range of natural alkaloids. Strategic application of this methodology and a late-stage radical cyclization as key steps have been showcased in the concise total synthesis of (-)-cephalocyclidin A.