Synthesis of 2-Arylpyridopyrimidinones, 6-Aryluracils, and Tri- and Tetrasubstituted Conjugated Alkenes via Pd-Catalyzed Enolic C-O Bond Activation-Arylation.

A new and efficient approach for the synthesis of biologically important 2-aryl-4H-pyrido[1,2-a]pyrimidin-4-ones and 6-aryluracils via previously unknown Pd-catalyzed enolic C-OH activation-arylation of pyridopyrimidin-2,4-diones and barbituric acids, respectively, with boronic acids is reported. The starting materials are readily available, and products are obtained in high yields. An efficient and chemo- and stereoselective access to various tri- and tetrasubstituted conjugated alkenones and alkenoates is also obtained in this arylation approach. Interestingly, the procedure for the construction of such diverse molecular frameworks is general and featured with excellent substrates scope, tolerance of a broad range of functionalities, the unusual viability of performing the reaction under open air and in aqueous cosolvent, and the amenability to a scale-up synthesis, which have been found to be common limitations in the conventional/classical routes. The application of the protocol in a simple one-step high-yield route to pharmaceutically important polyarylated pyridopyrimidinone demonstrates its further synthetic utility. [ABSTRACT FROM AUTHOR]