Modular assembly of chiral biaryl phosphoramidite (BPA) libraries by nickel catalysis

Chiral phosphoramidites have emerged as pivotal ligands in asymmetric catalysis, yet their synthesis has long been constrained by traditional de novo approaches. Here, we present a highly significant late-stage functionalization strategy, which facilitates the modular assembly of biaryl phosphoramidite (BPA) libraries. Leveraging P(iii)-directed C-H activation by nickel catalysis, we have developed a versatile platform for facile modification of the chiral pocket within these BPAs, enabling rapid structural optimization and exploration of diverse chemical architectures. These formed ligand libraries have demonstrated exceptional performance across a spectrum of asymmetric palladium-catalysed reactions, underscoring their broad applicability and potential. Through a synergistic combination of experimental investigations and computational analyses, we have elucidated the underlying reaction mechanism with remarkable clarity. This research not only furnishes advanced synthetic tools for the preparation of phosphoramidite libraries but also sets a new benchmark for the design and synthesis of novel ligands using state-of-the-art synthetic methodologies.