A general approach to phosphoramidites tethered with single and multiple linkers through the use of methoxyoxalamido (MOX) chemistry is described. The approach utilizes readily available and inexpensive primary aliphatic amino alcohols and diamines to produce a rich and diverse variety of tethered phosphoramidites. Furthermore, the use of MOX chemistry in a modular fashion enables fairly rapid assembly of compound tethers. All novel phosphoramidites described have been successfully used in automated syntheses of 5'-modified oligonucleotides.