2-Chloro-4-tetrafluorophenoxypyrimidine: a versatile reagent for C-2 prior to C-4 functionalizations. Issue 17 (27th April 2016)

• Record Type: Journal Article
• Authors: O'Donnell, Michael; Charrier, Jean-Damien
• Is Part Of: Tetrahedron letters. Volume 57:Issue 17(2016)
• Page Start: 1882
• Page End: 1884
• Publication Date: 2016-04-27
• Subjects: Pyrimidine -- Tetrafluorophenoxy -- Suzuki -- Negishi -- Sonogashira -- Regioselective functionalization; Chemistry, Organic -- Periodicals; 547.005
• DOI: 10.1016/j.tetlet.2016.03.057
• Languages: English
• ISSNs: 0040-4039

Abstract

Graphical abstract: Highlights: Description of uses of 2-chloro-4-tetrafluorophenoxypyrimidine. Description of its reactivity for the preparation of 2, 4-disubstituted pyrimidines. First functionalization occurs at C-2, under metal-catalyzed cross-coupling reactions. Second functionalization occurs at C-4, with aliphatic or aromatic amines. Approach offers complementary tool for the synthesis of pyrimidine-containing compounds. Abstract: A novel synthetic route to 2, 4-functionalized pyrimidines is reported. The approach uses 2-chloro-4-tetrafluorophenoxypyrimidine, that enables sequential palladium catalyzed functionalization at the pyrimidine C-2 position, followed by SN Ar displacement with diverse amines at C-4 . The broad utility of this ' C-2 then C-4 ' functionalization sequence has been demonstrated with a range of cross-coupling partners and amines.