Functionalisation of the uracil ring via palladium-catalysed aminocarbonylation.

Iodouracil derivatives (5-iodouracil, 5-iodo-1,3-dimethyluracil) were aminocarbonylated using a set of primary and secondary amines in the presence of in situ palladium(0) catalysts. The formation of carboxamides via single CO insertion was favoured at atmospheric CO pressure. The chemoselectivity toward double CO insertion can be increased by using 40 bar of CO pressure, in this way up to 60% selectivity toward 2-ketocarboxamide was achieved. In the case of 5-iodouracil the corresponding 5-glyoxylamido-uracil derivatives were exclusively formed at 40 bar CO pressure. The only exception is the less basic aniline nucleophile which provided the corresponding carboxamide exclusively. A typical side-reaction took place when 5-iodouracil was used as substrate: this heterocycle, existing in lactam-lactim tautomeric forms, underwent deiodination providing the parent uracil as side-product. Image 1 • Functionalisation of the uracil ring via palladium-catalysed aminocarbonylation. • Selective synthesis of 5-glyoxylamidouracil derivatives at high CO pressure. • Describing a proposed mechanism of deiodination side reaction. • Synthesis of uracil derivatives bearing amide moiety with biological importance. [ABSTRACT FROM AUTHOR]