Asymmetric Dipolar Cycloadditions toward Chiral Medium-Sized Rings under Palladium and Iridium Catalysis

Chiral medium-sized rings, defined herein as 7- to 11-membered cyclic frameworks, are common in bioactive molecules and occupy an important but still underexplored region of drug-like chemical space. Their asymmetric synthesis remains formidably challenging, as conformational flexibility, transannular interactions, and unfavorable entropic and enthalpic factors collectively complicate ring formation and stereocontrol. In recent years, palladium- and iridium-catalyzed asymmetric dipolar cycloadditions and related cascade processes have emerged as effective strategies for building structurally diverse and stereochemically complex medium-sized rings. As such, this review aims to summarize the advances in this emerging field from the perspectives of metal identity, precursor class, and dipole-generation mode, with emphasis on their effects on chemo-, regio-, diastereo-, and enantioselectivity. We also highlight the distinct yet complementary features of Pd and Ir catalysis, as well as current limitations in generality, selectivity, and substrate scope. By combining mechanistic insight with representative applications, this review aims to define the foundations, boundaries, and future opportunities of this rapidly evolving area.