Quantum Mechanical Investigations of Organocatalysis: Mechanisms, Reactivities, and Selectivities

B3LYP with modest basis sets continues to be used routinely for the study of organocatalysis, but deficiencies in this functional have been discovered. This is especially true for reaction thermochemistries and in cases where dispersion effects influence weak interactions between groups. Newer, more highly parametrized functionals such as Truhlar's M0X series, especially M06-2X and now M08 for organic reactions are being used routinely. More accurate, but also more expensive methods, like SCS-MP2, and double hybrid functionals like B2PLYP are being used with increasing frequency. Isoxazolidine-3-carboxylic Acid is an interesting choice of catalyst, due to the possibility of increased nucleophilicity originating from an α-effect. The Seebach-Eschenmoser model has been proposed to explain the origin of selectivity. This model involves the enamine carboxylate as a key reaction intermediate. Acyclic primary amino acids have also been discovered to be catalysts for the intermolecular aldol reactions.