Provided are methods of producing phosphitylated compounds, including
3'-O-phosphoramidites, comprising the step of reacting a
hydroxyl-containing compound with a phosphitylating agent in the presence
of a phosphitylation activator selected from the group consisting of: (1)
acid-base complexes derived from an amine base of Formula II 1
wherein R.sup.3, R.sup.4, R.sup.5, R.sup.6, and R.sup.7 are independently
hydrogen, C.sub.1-C.sub.10 alkyl, C.sub.3-C.sub.10 cycloalkyl,
C.sub.6-C.sub.10 aryl, C.sub.7-C.sub.10 aralkyl, C.sub.1-C.sub.10
heteroalkyl, or C.sub.1-C.sub.10 heteroaryl, and at least one of R.sup.3,
R.sup.4, R.sup.5, R.sup.6, and R.sup.7 is not hydrogen; (2) zwitterionic
amine complexes; and (3) combinations of two or more thereof, to produce
a phosphitylated compound. Further provided are methods for purifying
phosphitylated compounds comprising the steps of providing a
phosphitylated compound in a solution solvent, contacting said
phosphitylated compound with a precipitation solvent, and precipitating
said phosphitylated compound
