Asymmetric Diels–Alder Reaction Involving Dynamic Enantioselective Crystallization

Abstract

Asymmetric Diels-Alder reaction was achieved under achiral conditions. Reaction of prochiral 2-methylfuran and N-phenylmaleimide in heptane or hexane solution at 80 °C efficiently gave a conglomerate crystal of exo-type Diels-Alder adduct selectively, and continuous suspension of the reaction mixture with glass beads promoted attrition-enhanced deracemization, leading to an optically active exo-adduct in 90% ee.

Enantiospecific Solid Solution Formation Triggers the Propagation of Homochirality

“…the enantiomers interconvert into one another. [28][29][30][31] Based on the above analysis, we identified two families of compounds to test our hypothesis (Scheme 1). Compounds 1 a,b and 2 a,b crystallize as conglomerates and undergo complete chiral symmetry breaking under Viedma ripening conditions.…”

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

“…Recently, an asymmetric synthetic methodology has been developed that combines the generation of a chiral center from prochiral materials with deracemization via dynamic crystallization (Scheme ). Some valuable examples have been reported for the Mannich reaction, aldol reaction, desymmetrization from meso compounds via stereoisomerization, aza‐Michael addition reaction, Strecker reaction, photoisomerization followed by ring‐closing and ring‐opening reactions, photodimerization reaction, and Diels–Alder reaction . All processes involved deracemization by dynamic crystallization and either a reverse reaction or a direct racemization of the generated chiral center of the product…”

“…Some valuable examples have been reported for the Mannich reaction, [7] aldol reaction, [8] desymmetrization from meso compounds via stereoisomerization, [9] aza-Michaela ddition reaction, [10] Strecker reaction, [11] photoisomerization followed by ring-closing and ringopeningr eactions, [12] photodimerization reaction, [13] and Diels-Alder reaction. [14] All processes involved deracemization by dy-namic crystallization and either ar everse reaction or ad irect racemization of the generated chiralc enter of the product. [15] Here, we describe the asymmetrics ynthesis of amino acid derivatives using this methodology.…”

Enantiospecific Solid Solution Formation Triggers the Propagation of Homochirality

“…compounds that (a) crystallize as racemic conglomerates, and (b) racemize in the liquid phase, i.e. the enantiomers interconvert into one another [28–31] …”