Recent total synthesis of natural products leveraging a strategy of enamide cyclization

Abstract

Enamides are distinctive amphiphilic synthons that can be strategically incorporated into cyclization reactions. The iminium species generated from enamides via nucleophilic addition or substitution are capable of engaging in further electrophilic additions or isomerization processes. Exploiting the multiple reactivities of enamides facilitates the development of diverse cyclization modes that provide entries to various N-heterocycles, some of which serve as key structural motifs in natural alkaloids. This review highlights recent advancements in enamide-based cyclization reactions, including enamide–alkyne cycloisomerization, [3 + 2] annulation, and polycyclization, with a particular emphasis on their pivotal role as a strategy in the total synthesis of natural products.

Keywords

• alkaloid
• cyclization
• enamide
• natural product
• total synthesis