The stereoselective synthesis of sialic acid glycoconjugates is still a challenge in the field. Surprisingly, little is known on the regioselective O-substitution of sialic acids. Consequently, the effect of O-protecting groups and/or regioselectively protected building blocks on sialylations remains practically unexplored. O-Picoloyl protecting groups have emerged as novel substituents that have a profound effect on sialylations. Recently, high stereoselectivities were obtained by introducing picoloyl groups at the C-4 and C-7/C-8 positions. However, to understand the relationship between the position of the picoloyl group and its exact effect on sialylations, a convenient method to access to a wider range of regioselectively picoloylated building blocks is needed. Herein, a new method that provides an accessible route to a wide array of regioselectively acylated building blocks is reported. The regioselective introduction of picoloyl groups at various O-positions was achieved either by controlled direct picoloylation or by applying a modified ReSET methodology.