Direct Synthesis of Aryloxy Phosphonamidate Nucleotide Prodrugs Using the Cross Metathesis Assisted by Ultrasonic Irradiation

A direct synthetic strategy of aryloxy phosphonamidate nucleotide prodrugs (A, G, C, and U) was developed with the CM reaction assisted by ultrasonic irradiation and partitioned addition of 12 mol % of Hoveyda–Grubbs (H-G) II catalyst in 61–82% yields as a mixture of E-/Z-isomers (∼2:1) from aryloxy vinylphosponamidate and 5′-vinyl nucleoside moieties.