A process for the sysnthesis of oligonucleotides using
phosphoramidite chemistry is provided. The process employs as activator a 1,1-dioxo-1,2-dihydro-1λ6-benzo[d]isothiazol-3-one, preferably in the presence of an
organic base. The 1,1-dioxo-1,2-dihydro-1λ6-benzo[d]isothiazol-3-one is represented by the following
structural formula: wherein p is 0 or an integer from 1 to 4; X7 is O or S; R for each occurrence is a
substituent, preferably each independently, a halo, a substituted or unsubstituted aliphatic group, —NR11R12, —OR13, —OC(O)R13, —C(O)OR13, or cyano; or two adjacent R groups taken together with the carbon atoms to which they are attached form a six membered saturated or unsaturated ring; R11 and R12 are each, independently, —H, a substituted or unsubstituted aliphatic group, a substituted or unsubstituted
aryl group, or a substituted or unsubstituted aralkyl group; and R13 is a substituted or unsubstituted aliphatic group, a substituted or unsubstituted
aryl group, or a substituted or unsubstituted aralkyl group. Preferred organic bases are
pyridine, 3-methylpyridine, or N-methylimidazole.