title: Concise Xanthine Synthesis through a Double-Amidination Reaction of a 6-Chlorouracil with Amidines using Base-Metal Catalysis.
abstract: A new and concise route towards xanthines through a double-amidination reaction is described; consecutive intermolecular C-Cl and intramolecular oxidative C-H amidination. N-uracil amidines are obtained through SNAE on a 6-chlorouracil with amidines. Direct Cu-catalyzed oxidative C-H amidination on these N-uracil amidines yields polysubstituted xanthines. Sustainable oxidants, tBu2O2or O2, can be used in this oxidase-type reaction. The protocol allows for the introduction of N1, N3, N7, and C8 substituents during the xanthine-scaffold construction, thus avoiding post-functionalization steps. Both 6-chlorouracils and amidines are readily available commercially or through synthesis.
authors.affiliation: Organic Synthesis, Department of Chemistry, University of Antwerp, Groenenborgerlaan 171, 2020, Antwerp, Belgium.
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Morel
authors.affiliation: Organic Synthesis, Department of Chemistry, University of Antwerp, Groenenborgerlaan 171, 2020, Antwerp, Belgium.
authors.forename: Philippe
authors.initials: P
authors.lastname: Franck
authors.affiliation: Organic Synthesis, Department of Chemistry, University of Antwerp, Groenenborgerlaan 171, 2020, Antwerp, Belgium.
authors.forename: Johan
authors.initials: J
authors.lastname: Bidange
authors.affiliation: Organic Synthesis, Department of Chemistry, University of Antwerp, Groenenborgerlaan 171, 2020, Antwerp, Belgium.
authors.forename: Sergey
authors.initials: S
authors.lastname: Sergeyev
authors.affiliation: CatSci Ltd., CBTC2, Capital Business Park, Wentloog, Cardiff, CF3 2PX, United Kingdom.
authors.forename: Dan A
authors.initials: DA
authors.lastname: Smith
authors.affiliation: CatSci Ltd., CBTC2, Capital Business Park, Wentloog, Cardiff, CF3 2PX, United Kingdom.
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Moseley
authors.affiliation: Organic Synthesis, Department of Chemistry, University of Antwerp, Groenenborgerlaan 171, 2020, Antwerp, Belgium.
authors.forename: Bert U W
authors.initials: BU
authors.lastname: Maes
mesh_terms: D000578:Amidines / Q000737:chemistry*; D002384:Catalysis; D060326:Chemistry Techniques, Synthetic; D003300:Copper / Q000737:chemistry*; D016877:Oxidants / Q000737:chemistry; D010084:Oxidation-Reduction; D014498:Uracil / Q000031:analogs & derivatives* / Q000737:chemistry; D019820:Xanthine / Q000138:chemical synthesis* / Q000737:chemistry*
chemical_list: D000578:Amidines; D016877:Oxidants; D019820:Xanthine; C044976:6-chlorouracil; D014498:Uracil; D003300:Copper
keywords: amidination; base metal; cross-dehydrogenative reaction; oxidative C−H amination; xanthines