Transition-metal-catalyzed asymmetric functionalization of simple heterocycles: Facile access to chiral saturated heterocycles

Enantioenriched, substituted saturated heterocycles extensively occur in natural products, bioactive targets, and organic frameworks. Conventional tools for their synthesis often require engineered precursors that limit the flexibility of the synthetic routes and the diversity of target scaffolds. Therefore, the rapid and diverse synthesis of these heterocyclic molecules is highly desired yet challenging. Undoubtedly, the direct asymmetric functionalization of simple and readily accessible heterocyclic substrates represents one of the most straightforward and efficient solutions. Recently, innovative and modular strategies based on alkyl cross-coupling, directing-group-assisted C–H activation, photocatalytic hydrogen atom transfer (HAT), Heck reaction, and hydro- and difunctionalization have been designed to access chiral saturated heterocyclic motifs, paving the way for their more extensive utilization in future pharmaceuticals. In this perspective, recent progress in the preparation of chiral saturated heterocycles is outlined. How these innovations have enabled new levels of molecular selectivity, complexity, and practicality is also emphasized.