Stereochemistry of the DBU/LiCl-Assisted Nucleophilic Substitution at Phosphorus in Nucleoside-3‘-<i>O</i>-(<i>Se</i>-methyl Methanephosphonoselenolate)s<sup>†</sup>

The crystal and molecular structure of diastereomerically pure <i>N</i><sup>4</sup>-benzoyl-2‘-deoxycytidine 3‘-<i>O</i>-(<i>Se</i>-methyl methanephosphonoselenolate (FAST-eluted) (<b>4</b>, R = H, B = C<sup>Bz</sup>) and 5‘-<i>O</i>-pixylthymidine 3‘-<i>O</i>-(<i>S</i>-methyl methanephosphonothiolate (FAST-eluted) (<b>5</b>) have been elucidated by X-ray crystallography. The absolute configuration at the phosphorus atom in both compounds is <i>S</i><sub>P</sub>. Each <b>FAST-4</b>‘ (R = DMT, B = C<sup>Bz</sup>) and <b>FAST-5</b> (R = Px, B = Thy) in the process of DBU/LiCl-assisted condensation with 3‘-<i>O</i>-acetyl-<i>N</i><sup>4</sup>-benzoylcytidine and 3‘-<i>O</i>-acetylthymidine gave after deprotection (<i>S</i><sub>P</sub>)-dicytidine-(3‘,5‘)-methanephosphonate and (<i>S</i><sub>P</sub>)- dithymidine-(3‘,5‘)-methanephosphonate, respectively. Unambiguous assignment of the absolute configuration at the phosphorus in <b>4</b> (R = H, B = C<sup>Bz</sup>) and <b>5</b> (R = Px, B = Thy) allows for stereochemical correlation and the conclusion that DBU/LiCl-assisted nucleophilic substitution at phosphorus <i>occurs</i> <i>with</i> <i>net</i> <i>inversion</i> <i>of</i> <i>configuration</i>, in contrast to our earlier erroneous deduction. Moreover, the knowledge of the absolute configuration at the phosphorus atom in both <b>4</b> (R = H, B = C<b><sup>Bz</sup></b><sup></sup><b>)</b> and <b>5</b> (R = Px, B = Thy) allows for assignment of the absolute configuration at phosphorus in precursors of <b>4</b>‘ and <b>5</b>, such as 5‘-<i>O</i>-DMT-nucleoside 3‘-<i>O</i>- methanephosphonothioanilidates (<b>6</b>), methanephosphonoanilidates (<b>8</b>), and methanephosphonoselenoanilidates (<b>9</b>).