Synthesis of Phosphorodiamidate Oligonucleotide Dimers

Azido nucleosides couple with phosphoramidites via an initial iminophosphorane, which eliminates acrylonitrile to generate the coupled dimer P­(V) product. The vulnerable phosphite triester intermediate is bypassed entirely, making the methodology very suitable to solution-phase synthesis. This new coupling protocol requires no protection of the 5′-OH function and provides a new method of installing internucleosidic phosphorodiamidate bonds with near quantitative yields.