Entropy-driven asymmetric synthesis with chiral tethers

Abstract

The 2,4-pentanediol (PD)-tethered reaction is a stereocontrolled reaction having versatile applicability. When reactant and reagent elements are connected through a PD tether prior to their reaction, stereochemical purity of the product is very high for nine different types of reactions so far studied. Selectivity of one of the reactions shows temperature independency over a wide range from -78 to 150 °C, which indicates that the stereocontrol is driven by the entropy term. The strict stereocontrol of this reaction at high temperatures can be extended to vapor phase reactions performed above 250 °C. To understand how the two methyl groups on the PD tether stereocontrol the reaction, a new parameter, a chiral perturbation factor, is introduced. By this analysis, it is disclosed that the methyl groups promote an activation entropy change for both the diastereomeric processes, and the strict stereocontrol is achieved when the changes have opposite signs. © Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004.