New phosphoramidite reagent for phosphorylation of synthetic oligonucleotides in terminal position

Phosphoramidite I (1, R = iPr) useful as phosphorylation reagent in oligonucleotide syntheses, were prepd. by monomethoxytrityl protection of 4-​hydroxybenzaldehyde with subsequent borohydride redn. and phosphorylation with 2-​cyanomethyl N,​N-​diisopropylphosphoroamidochloridite. In an example, reaction of 5.08 g of 4-​hydroxybenzaldehyde with 1.0 g of 4-​methoxytriphenylmethyl chloride in 10 mL of dichloromethane in the presence of 2.2 mL of EtNiPr2 at 20° for 6 h gave the protected benzaldehyde, which was reduced with 0.25 g of NaBH4 in 10 mL of THF for 6 h at 20°, giving the protected benzyl alc., 4-​MMTO-​C6H4CH2OH with 85​% yield. The obtained product (0.23 g) was reacted with 0.2 mL of phosphoramidochloridite NCCH2CH2OP(Cl)​NiPr2in the presence of 0.4 mL of EtNiPr2 in 5 mL of CH2Cl2, giving the product 1 with 87​% yield.