Part I. Approaches Toward the Total Synthesis of Tyloindicine F; Part II. Palladium-Catalyzed C−H Functionalization of β-enaminones

Abstract

Tyloindicine F is a potent anticancer natural product first isolated from the Himalaya region of India. It demonstrated a unique profile in the NCI60 human tumor cell line anticancer drug screen. Due to its scarcity from natural sources, a total synthesis of tyloindicine F is desirable. Two attempts at the synthesis of this natural product have been conducted and are discussed. β-enaminones are a group of push-pull olefins whereas C-H functionalization/C-C coupling is a highly efficient method of constructing new carbon-carbon bonds. β-enaminones are highly polarized and their β; position is suitable for C-H functionalization by means of electropalladation. A novel methodology for the oxidative Hiyama coupling of β-enaminones has been developed and two new bifunctional activators/reoxidants have been found. Furthermore, a non-oxidative version for β-enaminone C-H functionalization and the decarboxylative coupling of β-enaminones were also investigated.