An olefin cross-metathesis approach to vinylphosphonate-linked nucleic acids

[GRAPHICS] The synthesis of vinylphosphonate-linked nucleotide dimers has been achieve d using an olefin cross-metathesis (CM) reaction as a key step. The 1,3-dim esityl-4,5-dihydroimidazol-2-ylidine-containing catalyst 5 (Grubbs' second- generation catalyst) was found to be the superior catalyst for this transfo rmation. Both metathesis partners were readily available using known method ology, and the vinylphosphonate-linked dimer was produced with high levels of (E)-selectivity (> 20:1) in 58% yield (70% based on recovered starting m aterial).