Thermodynamic and kinetic considerations in the chemoselective O-acylation by mixed anhydrides. A semiempirical MO approach

A simple methodology to achieve high chemoselective O-acylation of primary hydroxy groups, in the presence of secondary ones, was performed by means of the quick generation of a mixed anhydride using mild and inexpensive conditions. Steric and electronic factors are involved in this preference. As far as the geometries are concerned, semiempirical calculations were carried out in order to determine the nature of the contribution to the thermodynamics and kinetics. From a qualitative point of view, it was found that the thermodynamics are sugar dependent whereas the kinetics are mixed anhydride dependent. These conclusions fit quite well with the experimental results allowing the use of semiempirical MO calculations as a tool for modulating the selectivity ratio for this process since different systems may be modeled in the same way.