Methods and compositions are disclosed for the high yield chemical synthesis of 2'(3')-O-aminoacylated oligonucleotides, 2'(3')-O-aminoacylated pCpA derivatives and 2'(3')-aminoacyl-tRNA's. The present invention discloses the use of tetrahydrofuranyl group (THF) as a stable protecting group in the production of aminoacyl-oligonucleotides. THF can also be used in conjunction with a removable protecting group, such as dimethoxytrityl group (DMTr). The mild conditions employed for the removal of the THF group are compatible with the integrity of the aminoacyl linkage as well as tRNA, which makes it possible to utilize the methods of the present invention to form aminoacyl-tRNA's. The present invention discloses an efficient route for synthesizing 2'(3')-aminoacyl-pCpA, which can be used to load any natural amino acid, unnatural amino acid, labeled amino acid, reporter group or derivative thereof onto a tRNA molecule through an aminoacyl linkage.