Application of dimedone enamines as dienophiles: stereoselective synthesis of amino enols of fused uracils containing a sugar moiety by hetero-Diels–Alder reactions of barbituric acid 5-ylidene alditols with dimedone enamines

• Published in: Tetrahedron 2015-11, Vol.71 (47), p.8911-8924
• Main Authors: Pałasz, Aleksandra, Cież, Dariusz, Musielak, Bogdan, Kalinowska-Tłuścik, Justyna
• Format: Article
• Language: English
• Subjects: 1-Oxa-1,3-butadienes; Enamines; Hetero Diels–Alder reactions; Unprotected sugars; Uracils
• ISSN: 0040-4020; 1464-5416
• DOI: 10.1016/j.tet.2015.09.065

Dimedone enamines were applied for the first time as new dienophiles in hetero-Diels–Alder reactions with inverse electron demand. Cycloadditions of barbituric acid 5-ylidene alditols with dimedone enamines were performed in dichloromethane at room temperature for 3 days and fused uracils–chromeno[2,3-d]pyrimidine-2,4-diones were obtained in good 73–87% yields. Only one enantiomerically pure stereoisomer was obtained in each studied cycloaddition. Analysis of 1H NMR and 2D NMR spectra allowed for the determination that cycloadducts exist in solution as mixture of the neutral form and dipolar ion. The prepared fused uracils contain both amine and enol functional groups, so share amphiprotic properties and they are zwitterions in solid state. The new class of compounds–amino enols was synthesized, which similarly to amino acids exists as zwitterions. In obtained cycloadducts amino groups and sugar moieties are close each other and they both are in cis configuration and in axial position. It was also shown that different alkenes can be used as dienophiles towards barbituric acid 5-ylidene alditols, for example, styrene or 1-amino-2-thiocarbamoyl-cyclopent-1-ene. [Display omitted]