Dinuclear Metal‐ProPhenol Catalysts: Development and Synthetic Applications

The ProPhenol ligand is a member of the chiral aza-crown family that spontaneously forms a bimetallic complex upon treatment with alkyl metal reagents, such as Et₂ Zn and Bu₂ Mg. The resulting complex features Lewis acidic and Brønsted basic sites, enabling simultaneous activation of both nucleophile and electrophile in the same chiral environment. Since the initial report in 2000, metal-ProPhenol catalysts have been used to facilitate a broad range of asymmetric transformations, including aldol, Mannich, and Henry reactions, as well as alkynylations and conjugation additions. By promoting such a diverse array of reactions, these complexes provide rapid and atom-economical access to valuable complex building blocks. In this Review, we describe in detail the development and synthetic applications of these versatile catalysts with a special focus on recent efforts to improve reactivity and selectivity through ligand design and structural modification.