Prelog’s model as the first tool to predict stereoselectivity: identifying patterns in chemical data to construct models

Prelog’s model was one of the first empirical models to explain the stereoselectivity of the Grignard reactions of 2-oxocarboxylic acid esters bearing a chiral alcohol. Prelog constructed his model based on some assumptions regarding the conformation of chiral 2-oxocarboxylic acid esters to explain the relationship in configuration between the chiral alcohol starting materials and the 2-hydroxycarboxylic acid products. Construction of the model involves four steps: (1) mentally analyzing the reactants to identify the basic stereochemical structures, (2) assuming the conformations of the chiral alcohol moiety as the main reasons for stereoselectivity, (3) modeling the transition states to explain the relationship in configuration between the chiral alcohols and 2-hydroxycarboxylic acids, and (4) validating the evidence to revise the model. The process of constructing this historically pivotal model may have implications for science education, especially for developing theories from extensive data. The four steps from the Prelog’s model were compared with the models for boiling points of hydrocarbons and solubility of amino acids.