An efficient multi-component synthesis of N-1-alkylated 5-nitrouracils from α-amino acids. Issue 22 (1st June 2016)

• Record Type: Journal Article
• Authors: Boiteau, Jean-Guy; Bouix-Peter, Claire; Chambon, Sandrine; Clary, Laurence; Daver, Sebastien; Dumais, Laurence; Fournier, Jean-François; Harris, Craig S.; Mebrouk, Kenny; Millois, Corinne; Pierre, Romain; Rodeville, Nicolas; Talano, Sandrine; Tomas, Loïc
• Is Part Of: Tetrahedron letters. Volume 57:Issue 22(2016)
• Page Start: 2367
• Page End: 2371
• Publication Date: 2016-06-01
• Subjects: Multi-component reaction (MCR) -- Cyclocondensation -- 5-Nitrouracil; Chemistry, Organic -- Periodicals; 547.005
• DOI: 10.1016/j.tetlet.2016.04.039
• Languages: English
• ISSNs: 0040-4039

Abstract

Graphical abstract: Highlights: An efficient route to N -1-alkylated 5-nitrouracils from α-amino acids is disclosed. From a large reaction conditions' screen Cs2 CO3 was identified as the optimal base. In situ epimerisation during the cyclocondensation step is also controlled. Abstract: The preparation of N -1 selectively alkylated uracil intermediates usually requires selective protection at N -3 followed by alkylation at N -1 and subsequent removal of the protecting group. In this Letter, we show the limitations of this approach when quaternary C centres at N -1 became a key target for the programme. To access this key substructure, we developed an efficient multi-component reaction (MCR) from readily available α-amino acid precursors.