title: Organocatalyzed aldol reaction between pyridine-2-carbaldehydes and α-ketoacids: a straightforward route towards indolizidines and isotetronic acids.
abstract: Enantioselective aldol reactions between substituted pyridine carbaldehydes and α-ketoacids were shown to provide isotetronic acids or their corresponding pyridinium salts, depending on the nature of the substituents on the pyridine ring. The pyridinium salts were generated through nucleophilic attack of the pyridine nitrogen atom onto the reactive keto functional group. Moderate-to-good yields of both compounds were typically obtained and high levels of enantioselectivity were observed by using benzimidazole pyrrolidine I as a catalyst. Hydrogenation of the resulting pyridinium salts led to new indolizidines with high ee values and diastereocontrol. X-ray diffraction studies allowed the determination of the relative configuration of the products. Finally, DFT calculations were performed to rationalize the divergent pathway as a function of the pyridine substituents.
authors.affiliation: Université de Bordeaux, Institut des Sciences Moléculaires, UMR-CNRS 5255, 351, cours de la liberation, 33405 Talence Cedex (France), Fax: (+33) 540006286.
authors.forename: Virginie
authors.initials: V
authors.lastname: Liautard
authors.forename: Damien
authors.initials: D
authors.lastname: Jardel
authors.forename: Clotilde
authors.initials: C
authors.lastname: Davies
authors.forename: Muriel
authors.initials: M
authors.lastname: Berlande
authors.forename: Thierry
authors.initials: T
authors.lastname: Buffeteau
authors.forename: Dominique
authors.initials: D
authors.lastname: Cavagnat
authors.forename: Frédéric
authors.initials: F
authors.lastname: Robert
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Vincent
authors.forename: Yannick
authors.initials: Y
authors.lastname: Landais
mesh_terms: D000447:Aldehydes / Q000737:chemistry*; D001562:Benzimidazoles / Q000737:chemistry; D002384:Catalysis; D018360:Crystallography, X-Ray; D006865:Hydrogenation; D054836:Indolizidines / Q000737:chemistry*; D007651:Keto Acids / Q000737:chemistry*; D008968:Molecular Conformation; D011725:Pyridines / Q000737:chemistry*; D011759:Pyrrolidines / Q000737:chemistry; D013237:Stereoisomerism; D013816:Thermodynamics
chemical_list: D000447:Aldehydes; D001562:Benzimidazoles; D054836:Indolizidines; D007651:Keto Acids; D011725:Pyridines; D011759:Pyrrolidines; C432864:pyridine-2-carbaldehyde; C116609:3-hydroxybutanal; C031000:benzimidazole; C032519:pyrrolidine
keywords: aldol reaction; enantioselectivity; heterocycles; indolizidines; organocatalysis