The catalytic stereoselective synthesis of compounds with chiral phosphorous centers remains an unsolved problem. State-of-the-art methods rely on resolution or stoichiometric chiral auxiliaries. Phosphoramidite prodrugs are a critical component of pronucleotide (ProTide) therapies used in the treatment of viral disease and cancer. We will describe the development of a catalytic stereoselective method for the installation of phosphorus-stereogenic phosphoramidites to nucleosides through a dynamic stereoselective process. Detailed mechanistic studies and computational modeling led to the rational design of a multifunctional catalyst that enables stereoselectivity as high as 99:1.