Method for the synthesis of phosphorus atom modified nucleic acids

A method for the synthesis of a nucleic acid comprising a chiral X-phosphonate moiety comprising:

• reacting a molecule comprising an achiral H-phosphonate moiety, a chiral reagent, and a nucleoside comprising a 5′-OH moiety to form a condensed intermediate;
• and
• converting the condensed intermediate to the nucleic acid comprising a chiral X-phosphonate moiety, wherein:
• the nucleic acid comprises a modified sugar, wherein the modified sugar contains one or more substituents at the 2′-position selected from the group consisting of F, CF3, CN, N3, NO, NO2, O-, S-, or N-alkyl;
• O-, S-, or N-alkenyl;
• O-, S-, or N-alkynyl;
• or O-alkyl-O-alkyl, O-alkyl-N-alkyl or N-alkyl-O-alkyl wherein the alkyl, alkenyl and alkynyl may be substituted or unsubstituted C1-C10 alkyl or C2-C10 alkenyl and alkynyl;
• each instance of X is independently alkyl, alkoxy, aryl, alkylthio, acyl, —NRfRf, alkenyloxy, alkynyloxy, alkenylthio, alkynylthio, —S−Z+, —Se−Z+, or —BH3−Z+;
• each instance of Rf is independently hydrogen, alkyl, alkenyl, alkynyl, or aryl;
• Z+ is ammonium ion, alkylammonium ion, heteroaromatic iminium ion, or heterocyclic iminium ion, any of which is primary, secondary, tertiary or quaternary, or Z+ is a monovalent metal ion.