Generation of Highly Enantioenriched Crystalline Products in Reversible Asymmetric Reactions with Racemic or Achiral Catalysts

Abstract

Rückwärts zum Ziel: Ausgehend von einem Konglomerat von 1 mit niedrigem Enantiomerenüberschuss werden in Gegenwart racemischer oder achiraler Katalysatoren asymmetrische Verstärkungen von bis zu 100 % ee erzielt, wenn man Vorwärts‐ und Rückwärtsreaktionsschritte eines reversiblen chemischen Prozesses (siehe Schema) mit den physikalischen Prozessen der Kristallisation, Kristallzermahlung und Auflösung verbindet.

The Origin of Biological Homochirality

“…This was successfully shown recently for an amino acid derivative (Noorduin at al. 2008), for the proteinogenic amino acid aspartic acid (Viedma et al 2008) (Scheme 2), and for a Mannich reaction product (Tsogoeva et al 2009). …”

Total Spontaneous Resolution by Deracemization of Isoindolinones

“…[1] To resolve optically active materials by crystallization efficiently, dynamic preferential crystallization involving a racemization process, a so-called total spontaneous resolution, has been developed. [5][6][7] We have now developed a new example of total spontaneous resolution of isoindolinones that involves a combination of an intramolecular equilibrium reaction via an achiral intermediate and preferential crystallization.Various heterocyclic compounds containing the isoindolinone skeleton have important biological activities, and many of these have been prepared and examined as pharmaceutical agents. [5][6][7] We have now developed a new example of total spontaneous resolution of isoindolinones that involves a combination of an intramolecular equilibrium reaction via an achiral intermediate and preferential crystallization.…”

On the Physical Basis of Asymmetry and Homochirality

“…The operational protocol can be executed under different variations; especially, the presence of a catalyst is often required to promote the solution‐phase racemization. It should also be mentioned that recent examples also include enantioenriched products from chemical reactions such as reversible aldol or Mannich reactions with racemic or achiral catalysts . Such results illustrate the potentiality of this methodology; however, they introduce further complications.…”