Controlling Isomerization by High-Resolution Reaction Time Control

Abstract

When a reactive intermediate can be isomerized and the isomerized intermediate can further react to give an isomer of an intended product, setting a shorter residence time will suppress such isomerization and allow highly selective synthesis of an intended product. The rate of isomerization is also temperature dependent, and thus, controlling not only the residence time but also the temperature is important. In some cases, the isomerization may proceed completely to give a more stable isomer of the reactive intermediate. In such cases, high-resolution reaction time control allows selective synthesis of either a product derived from the initial intermediate or a product derived from the isomerized intermediate at will. When isomerization of an intermediate gives an equilibrium mixture, setting a shorter residence time will suppress such isomerization and allow highly selective synthesis of a product derived from the intermediate that has yet to be isomerized. This concept basically can be applied to positional isomers and stereoisomers. In particular, this concept is useful in asymmetric synthesis in which epimerization of an optically active intermediate can be suppressed to allow synthesis of a product with high enantiomeric purity.