title: Non-racemic atropisomeric (thio)ureas as neutral enantioselective anion receptors for amino-acid derivatives: origin of smaller Kass with thiourea than urea derivatives.
abstract: The synthesis of a limited series of non-racemic atropisomeric 1-(2-(4-methyl-2-thioxothiazol-3(2H)-yl)phenyl)-3-(hetero)aryl-(thio)ureas is described. Using NMR titration experiments monitoring the shift of the two NH of the (thio)urea and the C-5 hydrogen of the heterocycle, the binding constants for some optically pure (thio)-ureas with the enantiomers of N-protected amino acid tetrabutylammonium salts were determined in CD3CN. The obtained enantioselectivities were modest. Contrary to what was expected on the basis of the NH acidity in thiourea versus urea group, the association constants were smaller with the thiourea than with the corresponding urea. X-ray data, DFT calculations, and NMR provided the explanation of that unexpected behavior: the urea presents a pre-organized (Z,Z) conformation suitable for a double hydrogen bond with the carboxylate anion, the thiourea presents a (Z,E) conformation, which must be reorganized in a constrained (Z,Z) conformation in the complex. An intramolecular hydrogen bond between one NH and the thiocarbonyl group of the heterocycle, which is present in the thiourea and absent in the urea, might also contribute to the smaller K(ass) for the thiourea. The possible implication of these observations in the field of bifunctional organocatalysis is briefly discussed.
authors.affiliation: Laboratoire Stéréochimie dynamique et Chiralité, UMR 6180, Chirotechnologies, catalyse et biocatalyse, CNRS-Université Paul Cézanne-Aix-Marseille III, Marseille, France. christian.roussel@univ-cezanne.fr
authors.forename: Christian
authors.initials: C
authors.lastname: Roussel
authors.forename: Mihaela
authors.initials: M
authors.lastname: Roman
authors.forename: Federico
authors.initials: F
authors.lastname: Andreoli
authors.forename: Alberto
authors.initials: A
authors.lastname: Del Rio
authors.forename: Robert
authors.initials: R
authors.lastname: Faure
authors.forename: Nicolas
authors.initials: N
authors.lastname: Vanthuyne
mesh_terms: D000596:Amino Acids / Q000737:chemistry*; D000838:Anions / Q000737:chemistry*; D002482:Cellulose / Q000031:analogs & derivatives / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid; D006860:Hydrogen Bonding; D009682:Magnetic Resonance Spectroscopy; D000432:Methanol / Q000737:chemistry; D008958:Models, Molecular; D008968:Molecular Conformation; D012997:Solvents / Q000737:chemistry; D013237:Stereoisomerism; D013890:Thiourea / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D014508:Urea / Q000737:chemistry* / Q000378:metabolism; D014961:X-Ray Diffraction
chemical_list: D000596:Amino Acids; D000838:Anions; D012997:Solvents; C070231:Chiracel OJ; D014508:Urea; D002482:Cellulose; D013890:Thiourea; D000432:Methanol