The Isoinversion Principle-a General Model of Chemical Selectivity

A large number of successful methods for chirality transfer, using either stoichiometric or catalytic chiral auxiliaries, are in use today. However, there is a lack of practical and dynamic selectivity models, i.e. models which take into account the entire reaction sequence, and which allow simple and reliable assessment, optimization and prediction of selectivity in asymmetric syntheses. The models that are available are either too strongly biased to the steric requirement of the particular molecules reacting, but do not go beyond classical considerations of static facial differentiation, or they take a demanding, theoretical approach, which because of its inherent limitations and the great theoretical effort required has not yet found its way into the practical world of the synthetic chemist. The “Isoinversion Principle”, developed on the basis of Eyring's theory, closes this gap. With its aid, the synthetic chemist can determine the characteristic isoinversion temperature Ti for the reaction type of interest from a few temperature‐dependent measurements of selectivity parameters. Ti then affords information on interesting questions such as optimization etc. The advantage of this method is that it is useful not only for stereoselectivity, but for any kind of process where selectivity in general (regio‐,chemo‐, etc) is generated at two or more stages of a reaction sequence, regardless of whether these reactions involve the ground state or a diabatic photoprocess. The present review will demonstrate that this generation of selectivity at two or more stages of a reaction sequence occurs more commonly than is generally thought. Competition between enthalpy and entropy is the reason why many reactions in which selectivity plays a role in more than one step display a strongly temperature‐dependent overall selectivity with an inversion point. Analysis of the activation parameters at various temperatures for the reaction of interest according to the isoinversion principle yields an “inversion temperature”, which may be used as a parameter to characterize the overall selectivity of the reaction. Such analyses also afford insight into the reaction mechanism.