Practical and convergent syntheses of 2'-deoxy-1',2'-seco-nucleophosph
onates and 1',2'-seco-nucleophosphonates are described. Phosphonate ch
irons derived from D-isoascorbic acid were used in alkylation of funct
ionalized nucleobases to provide the title phosphonate isosteres in go
od yields. Subsequent deprotection and deesterification led to the 5'-
C-methylenephosphonic acids which were conveniently purified using gra
vity flow C-18 reverse phase column chromatography.