Absolute Asymmetric Synthesis of an Aspartic Acid Derivative from Prochiral Maleic Acid and Pyridine under Achiral Conditions

Abstract

The asymmetric synthesis of an aspartic acid derivative, N‐succinopyridine, from prochiral starting materials involving dynamic enantioselective crystallization was accomplished without using any external chiral source. The aza‐Michael addition reaction of prochiral maleic acid and pyridine afforded racemic conglomerate N‐succinopyridine in water. Continuous stirring of the suspension of the reaction mixture with acetic acid promoted gradual deracemization to afford a crystal with an excellent optical purity of 99 % in 71 % yield.

Helical Networks of π‐Conjugated Rods – A Robust Design Concept for Bicontinuous Cubic Liquid Crystalline Phases with Achiral Ia3¯d and Chiral I23 Lattice

“…Spontaneous emergence of chirality during self-assembly is also of paramount interest for circularly-polarized emission [46][47][48] and photonic applications, [27,28] and for new dynamic routes to absolute enantioselective synthesis. [156][157][158]…”

Spontaneous Deracemizations

“…However, other racemization procedures, through a redox reaction, thermal sigmatropic rearrangement, atropisomerism, and photoisomerization , are being reported. The efficiency of the deracemization and its compatibility in the Viedma procedure have been used for direct absolute asymmetric synthesis and one-pot procedures. ,, In summary, Viedma deracemization is on the way to become part of retrosynthetic analysis for absolute asymmetric synthesis. , Experimental reports improving the mechanical crystal attrition ,− or using other types of selective energy, for example, temperature gradients and temperature cycles, ,,− ultrasound, and photochemical catalysis . These reports indicate that supersaturation for the bigger crystals is a necessary condition to generate permanent recycling through the initial crystal growth stages.…”

“…However, other racemization procedures, through a redox reaction, thermal sigmatropic rearrangement, atropisomerism, and photoisomerization , are being reported. The efficiency of the deracemization and its compatibility in the Viedma procedure have been used for direct absolute asymmetric synthesis and one-pot procedures. ,, In summary, Viedma deracemization is on the way to become part of retrosynthetic analysis for absolute asymmetric synthesis. , …”

“…164,210,211 In summary, Viedma deracemization is on the way to become part of retrosynthetic analysis for absolute asymmetric synthesis. 212,213 (c) Experimental reports improving the mechanical crystal attrition 153,214−220 or using other types of selective energy, for example, temperature gradients and temperature cycles, 182,183,221−224 ultrasound, 225 and photochemical catalysis. 226 These reports indicate that supersaturation for the bigger crystals is a necessary condition to generate permanent recycling through the initial crystal growth stages.…”

Attrition-Enhanced Deracemization and Absolute Asymmetric Synthesis of Flavanones from Prochiral Precursors

“…In recent years, asymmetric transformations using naturally generated crystal chirality have provided chiral symmetry breaking of racemic mixtures by dynamic crystallization, − and absolute asymmetric synthesis from a prochiral substrate to form an asymmetric center that racemizes into a product with high enantiomeric purity. − Some novel examples have been demonstrated, such as an asymmetric aza-Michael addition involving the racemization of the products leading to enantiomorphic crystals. − Products with very high enantiomeric purity were successfully obtained from prochiral materials. Here, we designed a new reaction protocol for the absolute asymmetric synthesis of flavanones, as shown in Figure , in which flavanone 4 can be obtained by aldol condensation of an achiral 2-hydroxyacetophenone 1 and an aromatic aldehyde 2 , followed by intramolecular oxa-Michael addition.…”