The Size‐Accelerated Kinetic Resolution of Secondary Alcohols

Abstract

The factors responsible for the kinetic resolution of alcohols by chiral pyridine derivatives have been elucidated by measurements of relative rates for a set of substrates with systematically growing aromatic side chains using accurate competitive linear regression analysis. Increasing the side chain size from phenyl to pyrenyl results in a rate acceleration of more than 40 for the major enantiomer. Based on this observation a new catalyst with increased steric bulk has been designed that gives enantioselectivity values of up to s = 250. Extensive conformational analysis of the relevant transition states indicates that alcohol attack to the more crowded side of the acyl-catalyst intermediate is favoured due to stabilizing CH-p-stacking interactions. Experimental and theoretical results imply that enantioselectivity enhancements result from accelerating the transformation of the major enantiomer through attractive non-covalent interactions (NCIs) rather than retarding the transformation of the minor isomer through repulsive steric forces.

Noncovalent CH–π and π–π Interactions in Phosphoramidite Palladium(II) Complexes with Strong Conformational Preference

“…When combined, such interactions provide substantial stabilization of supramolecular host–guest complexes, aid in folding of extended molecules, enhance the binding of a catalyst with a substrate, or stabilize one diastereomeric transition state with a chiral reagent or a catalyst more than the other state(s). Currently, an extensive effort is devoted to designing dispersive interacting sites in molecules to exploit the elements essential for controlling conformation, binding, and reactivity in a predictable way in the area of asymmetric organocatalysis [2–8] . Moreover, quantification of weak interactions in terms of energy is highly desirable for the design of remarkably effective catalysts.…”

Size‐Induced Inversion of Selectivity in the Acylation of 1,2‐Diols

“…In kinetic resolution experiments and other 1 : 1 competition experiments it is common practice to select a single conversion point for the determination of relative reaction rates, often at conversions of around 50 %. [ 5d , 16 , 17 , 24 ] However, in order to limit the influence of the second acylation step on the ratio of the mono‐acylation, the 30 % conversion point seems more appropriate. From these measurements we derived the relative rate constant k rel,a30% defined as the ratio between the concentrations of monoesters 2b(a – g) and 3b(a – g) (Figure 2 b, for more details see Supporting Information).…”

Die größenbeschleunigte kinetische Racematspaltung sekundärer Alkohole

“…Diese Arbeit wurde finanziell von der Deutschen Forschungsgemeinschaft (DFG) im Schwerpunktprogramm "Control of London Dispersion Interactions in Molecular Chemistry" (SPP 1807) unterstützt. Wir danken Dr. Peter Mayer für das Messen und Berechnen der Rçntgenstruktur-analysen [37] und dem Leibniz-Rechenzentrum (LRZ) für die großzügige Bereitstellung von Rechenkapazitäten. Open Access Verçffentlichung ermçglicht und organisiert durch Projekt DEAL.…”