Enantioseparation of Sulfoxides and Nitriles by Inclusion Crystallization with Chiral Organic Salts Based on l‐Phenylalanine

Abstract

Enantioselective inclusion of aromatic sulfoxides and nitriles was achieved in a host framework created by organic salts comprising achiral benzoic acids and a chiral primary amine (1a) derived from l‐phenylalanine. Tuning of the combined achiral acid component successfully changed the chiral recognition ability of the organic salts. The guest molecules were hydrogen‐bonded to form three‐component inclusion crystals, and the enantiomers of nitriles and sulfoxides were separated with high selectivity up to 92 and 98 % ee. As far as we know, this is the first example of the enantioseparation of non‐functionalized aromatic nitriles.

Enantiomer Separation of Nitriles and Epoxides by Crystallization with Chiral Organic Salts: Chirality Switching Modulated by Achiral Acids

“… a Nitriles (5 equiv) were used. b The inclusion ratio was determined by 1 H NMR analysis. c Yield of crystal was calculated based on the initially used 2 . d Yield of guest was calculated based on half the amount of initially used 3 . e ee was determined by HPLC analysis. Absolute configuration of the major enantiomer is shown in the parentheses. f Previously reported in ref . …”

“…All reagents and solvents were purchased and used as received. Achiral carboxylic acids were commercially available, except for 1c , which was synthesized according to the reported procedure. , Chiral amines ( 2 ) were synthesized from the corresponding natural amino acids and anilines . Racemic nitriles ( 3 ) were synthesized according to the reported method .…”

“…Achiral carboxylic acids were commercially available, except for 1c , which was synthesized according to the reported procedure. , Chiral amines ( 2 ) were synthesized from the corresponding natural amino acids and anilines . Racemic nitriles ( 3 ) were synthesized according to the reported method . Racemic epoxides ( 4 ) were synthesized via the oxidation of the corresponding styrenes, according to the general procedure.…”

“…We have been studying the enantioseparation of alcohols and sulfoxides by diastereoselective inclusion crystal formation with primary ammonium-carboxylate organic salts as chiral host compounds. − One diastereomeric ternary cocrystal was preferentially obtained over the other diastereomeric cocrystals. Recently, we reported enantioselective inclusion of non-functionalized nitriles with a chiral organic salt between 4-hydroxybenzoic acid ( 1a ) and a chiral primary amine ( 2a ) derived from l -phenylalanine with a hydrazide group . When the salt 1a·2a was recrystallized from a solution in the presence of racemic nitriles ( 3 ), ( S )- 3 was preferentially included in the deposited salt crystal.…”

Chiral Cocrystal Solid Solutions, Molecular Complexes, and Salts of N-Triphenylacetyl-l-Tyrosine and Diamines

“…Dipeptides such as di-L-phenylalanine build firm supramolecular systems with a solvent molecule, which are potentially useful in developing new nanomaterials [37]. Organic salts consisting of simple derivatives of L-phenylalanine and achiral carboxylic acids create host-frameworks capable of enantioseparation of sulfoxides and nitriles [38]. Amino acids are also subjects in exploration of the enantiodiscrimination processes utilizing zinc complexes, gold nanoparticles, β-cyclodextrine, and resorcin [4] arenes derivatives [39,40,41,42].…”