Novel water-soluble phosphatriazenes: versatile ligands for Suzuki-Miyaura, Sonogashira and Heck reactions of nucleosides

Two new water-soluble phosphatriazene ligands have been synthesized as versatile ligands for complexation reactions with Pd(OAc) 2 and utilized for catalyzing column-free Suzuki-Miyaura cross-coupling of various purine and pyrimidine halonucleosides in water. The water-solubility of the catalytic system simplified the isolation of the cross-coupled products to mere filtration, while the catalytically active solution in the filtrate was recycled eight times. A novel copper-free Sonogashira coupling protocol for the nucleosides has also been established via a one-pot synthesis of FV-100, a nucleoside-based drug in phase 3 clinical trials for herpes zoster or shingles treatment. Application of the Heck reaction was demonstrated by the synthesis of another antiviral drug: BVDU. Two new water-soluble phosphatriazene as versatile ligands for catalyzing Suzuki-Miyaura reactions of purines and pyrimidines in neat water with the possibility of recycling. Copper-free Sonogashira and Heck reaction were also made possible.