Novel 2- and 4-substituted pyrimidine nucleosides and oligonucleosides are provided, as are methods and intermediates useful in preparing same. In preferred embodiments, one of the 2- and 4-substituents is =O, =NH, or =NH2+ and the other is Q, =C (RA)-Q, C(RA)(RB)-C(RC)(RD)-Q, C (RA)=C(RC)-Q or C 3BOND C-Q, where RA, RB, RC and RD independently are H, SH, OH, NH2, or C1-C20 alkyl, or one of (RA)(RB) or (RC)(RD) is =O, and Q is halogen, hydrogen, C1-C20 alkyl, C1-C20 alkylamine, C1-C20 alkyl-N-phthalimide, C1-C20 alkylimidazole, C1-C20 alkylbis-imidazole, imidazole, bis-imidazole, amine, N-phthalimide, C2-C20 alkenyl, C2-C20 alkynyl, hydroxyl, thiol, keto, carboxyl, nitrates, nitro, nitroso, nitrile, trifluoromethyl, trifluoromethoxy, O-alkyl, S-alkyl, NH-alkyl, N-dialkyl, O-aralkyl, S-aralkyl, NH-aralkyl, azido, hydrazino, hydroxylamino, isocyanato, sulfoxide, sulfone, sulfide, disulfide, silyl, O-(hydroxyl protecting group), a leaving group, a heterocycle, an intercalator, a reporter molecule, a conjugate, a polyamine, a polyamide, a polyethylene glycol, a polyether, or a depurination enhancing group.