A process for the preparation of phosphorothiotriesters of structure IIIc comprising the steps of: i) reacting an H-phosphonate of structure lc with a silylation reagent to provide a silyloxyphosphonate； ii) reacting the silyloxyphosphonate with a bis (thiosulfonate) reagent of structure IVc to provide a phosphorothiotylester comprising a thiosulfonate group of structure Vc； iii) reacting the phosphorothiotylester comprising a thiosulfonate group of structure Vc with a nucleophile of structure VIc to provide the phosphorothriotyesters of structure IIIc； wherein, the H-phosphonate of structure lc has the following structure: ** Formula ** in which, W is independently selected from O, S, NH or CH2； R3 is -OH, -SH, -NRdRd, -N3, halogen, hydrogen, alkyl, alkenyl, alkynyl, alkyl-Y1-, alkenyl-Y1-, alkynyl-Y1-, aryl-Y1-, - P (O) (Re) 2 ,, -HP (O) (Re), -ORa or -SRc； Y1 is O, NRd, S or Se； Ra is a blocking group； Rc is a blocking group； each instance of Rd is independently hydrogen, alkyl, alkenyl, alkynyl, aryl, acyl, substituted silyl, carbamate, -P (O) (Re) 2 or -HP (O) (Re)； each instance of Re is independently hydrogen, alkyl, aryl, alkenyl, alkynyl, alkyl-Y2-, alkenyl-Y2-, alkynyl-Y2-, aryl-Y2-, or heteroaryl-Y2-, or a cation that is Na + 1, Li + 1 or K + 1； each instance of R4 is independently hydrogen, -OH, -SH, -NRdRd, -N3, halogen, alkyl, alkenyl, alkynyl, alkyl-Y1-, alkenyl-Y1-, alkynyl-Y1-, aryl-Y1-, heteroaryl- Y1-, -ORb or -SRc, and Rb is a blocking group； each instance of Ba is independently an adenine, cytosine, guanine, thymine, uracil, or modified, blocked, or unblocked nitrogenous base； Y2 is O, S or NRd where Rd is hydrogen, alkyl, alkenyl, alkynyl, aryl, acyl, substituted silyl or carbamate； R5 is hydrogen, a blocking group, a binding moiety connected to a solid support or a binding moiety connected to a nucleic acid； and n is between 1 and about 200； and the bis (thiosulfonate) reagent of structure IVc has the following structure: ** Formula ** in whic
