Chiral phosphoric acid catalyzed asymmetric synthesis of C–N axially chiral uracils with antitumor activity through kinetic resolution strategy†

An efficient method for the asymmetric synthesis of C–N axially chiral uracils has been developed by kinetic resolution of 6-NH₂-substituted uracils with achiral azlactones, using chiral phosphoric acid-catalyzed asymmetric acylation. A broad range of 6-NH₂ uracils were resolved with high efficiency and enantioselectivity, achieving a selectivity factor of up to 276. DFT calculations revealed the origins of the enantioselectivity. Large-scale reaction and straightforward transformations of the chiral products highlighted the practical value of this methodology. Furthermore, potential antitumor agents were identified through cellular assays, illustrating the synthetic utility of this approach.