2) The chosen substituents are small enough to be well described by high-level methods and eliminate as much uncertainty as possible due to compromises in level of theory. The goal of our results is that the electronic structure trends are informative and reliable enough to guide the intuition of more practical isocyanate applications. This tight range seems to indicate that the size of the substituent has only minor influence on the reaction barrier, which is not surprising as Zhao and Suppes came to similar conclusions considering the size of the reacting alcohol. In TS1 and TS2, the substituents are opposite from the active site of the reaction and have no proximity to any moieties that might result in steric hindrance. The one exception to this might be the R=COH B case, as the substituent hydroxyl group is oriented towards the isocyanate oxygen, resulting in a favorable intramolecular interaction.